JP2016006414A - Inspection system, inspection method, and inspection base - Google Patents

Inspection system, inspection method, and inspection base Download PDF

Info

Publication number
JP2016006414A
JP2016006414A JP2015104817A JP2015104817A JP2016006414A JP 2016006414 A JP2016006414 A JP 2016006414A JP 2015104817 A JP2015104817 A JP 2015104817A JP 2015104817 A JP2015104817 A JP 2015104817A JP 2016006414 A JP2016006414 A JP 2016006414A
Authority
JP
Japan
Prior art keywords
liquid
rotation
example
inspection
drainage
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
JP2015104817A
Other languages
Japanese (ja)
Inventor
田代 英夫
Hideo Tashiro
英夫 田代
野田 紘憙
Hiroyoshi Noda
紘憙 野田
伊藤 嘉浩
Yoshihiro Ito
伊藤  嘉浩
Original Assignee
株式会社コンソナルバイオテクノロジーズ
Consonal Biotechnologies Co Ltd
国立研究開発法人理化学研究所
Institute Of Physical & Chemical Research
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to JP2014108536 priority Critical
Priority to JP2014108536 priority
Application filed by 株式会社コンソナルバイオテクノロジーズ, Consonal Biotechnologies Co Ltd, 国立研究開発法人理化学研究所, Institute Of Physical & Chemical Research filed Critical 株式会社コンソナルバイオテクノロジーズ
Priority to JP2015104817A priority patent/JP2016006414A/en
Publication of JP2016006414A publication Critical patent/JP2016006414A/en
Application status is Pending legal-status Critical

Links

Abstract

[PROBLEMS] To improve determination accuracy, inspection time, operability, and safety.
[Solution]
A turntable (1), a test substrate (S2) supported by the turntable (1), a storage section (A1) capable of storing a liquid test sample (L0), and a storage section (A1) And the spot (103) that reacts with the test sample (L0), the drainage part (A2) outside the accommodating part (A1) with respect to the rotation center (2) of the turntable (1), and the accommodating part ( The inspection base (S2) having a separation part (102) for separating A1) and the drainage part (A2), the rotational drive mechanism (4) of the turntable (1), and the cleaning liquid (L1) are accommodated. A supply unit (22) for supplying to the unit (A1), a drainage control means (C2) for draining by rotating the turntable (1) at a rotational speed (N2, N3) on which centrifugal force acts, and a cleaning liquid An observation member (43) for observing the spot (103) when (L1) is drained from the container (A1).査 system (S).
[Selection] Figure 1

Description

  The present invention relates to an inspection system, an inspection method, and an inspection substrate that can be used in an on-the-spot clinical test, a so-called Point Of Care Testing (POCT).

  Allergic diseases include hay fever, atopic dermatitis, bronchial asthma, food allergies and drug allergies, and various allergic diseases are known. In recent years, of the 120 million people, it is said that there are 42 million people who have some kind of relationship with allergies, and the number is increasing. As the reason why the number of patients with allergic diseases has increased in this way, the increase in the sensitizing substance (antigen) in the daily living environment and the concentrated exposure to the sensitizing substance are said to be the largest factors. Since allergic diseases cannot be separated from the daily living environment, it is not sufficient to treat symptoms with drugs, and relapse cannot be avoided. Therefore, it is important to go to the cause and identify the causative substance for treatment. Therefore, in the allergy department, dermatology department, internal medicine department, etc. of a medical clinic, a diagnosis for identifying an antigen that is a causative substance that causes allergic symptoms, that is, an allergen, is indispensable in medical treatment related to allergic diseases. However, there are many types of allergen substances, more than 200 types. Therefore, in order to identify allergens in them, it is indispensable to examine multiple types of allergen species.

  Here, the allergy occurrence mechanism will be briefly described. The allergic symptom is an antigen-antibody reaction in which an antigen acts on the body (living body) and an immune function works. As a result of this reaction, immunoglobulin (abbreviated as “Immunoglobulin”) is produced. An immunoglobulin is a protein and its structure is a chain of amino acids. Currently, there are five known immunoglobulins: A, G, D, M, and E. Of these, it is known that excessive reaction of E-type immunoglobulin E (abbreviated as IgE) causes allergic symptoms. It has been. In other words, when IgE is produced, so-called sensitization in which IgE binds to mast cells in blood or the like is established. When antigen further invades after establishment of this sensitization, IgE bound to mast cells binds to the antigen, and chemical mediators such as histamine are released from the mast cells, causing allergic symptoms. Since antibodies recognize molecules and react, different IgE (abbreviated as specific IgE) is produced for each allergen species, and the sensitization state differs for each allergen (Non-Patent Document 1, Non-Patent Document 1, Non-patent Document 1). Patent Document 2).

  One method for identifying allergens is a skin provocation test in which allergens are added directly to the skin. In the prick test as an example of the skin induction test, the allergen is dripped onto the skin surface and the skin surface is scratched with a needle so that the allergen is absorbed by the body. This confirms the reaction to the allergen. Such a skin induction test is highly accurate in that the reaction to the allergen can be directly confirmed. However, there is a fear of anaphylactic shock and the like, and there is a risk of putting the patient at risk (Non-patent Document 3). Therefore, in recent years, test tube tests that collect blood from patients and measure the amount of IgE in serum are widely used due to their low burden and ease of testing.

  In a test tube test that measures the amount of IgE, the allergen species-specific IgE concentration in the blood is measured to identify sensitized allergens. Specific allergen concentration is very small, positive (Class 2) if it is 1.68 [ng / mL] or more, false positive (Class 1) if it is 0.84 [ng / mL] or more, negative (Class 0) ). The standard classification is that it is divided into 7 levels up to 240 [ng / mL] or more strong positive (class 6).

  There are various IgE detection methods such as the CAP method and the MAST method. The basic measurement principle of these allergen-specific IgE calibration methods is the same. That is, the target specimen is allowed to act on the carrier surface on which the allergen is immobilized, and the specimen IgE reacts with the allergen. Thereafter, IgE derived from the specimen that reacts with and binds to the allergen is reacted with an anti-IgE antibody that can bind to the IgE antibody to detect the anti-IgE antibody. Thereby, measurement of IgE amount is possible. The anti-IgE antibody is labeled, and a fluorescent molecule, a chemiluminescent molecule, a chemical coloring molecule or a radioisotope is used for the labeling.

  The CAP method commercialized by Phadia is currently the most popular allergen-specific IgE calibration method in the world. In this method, one well is used as a carrier for one type of allergen, and one sample is added thereto, and the presence or absence of IgE antibody against the allergen fixed in the well is determined. In other words, the CAP method is a single item method. Therefore, since only one type of allergen can be determined per well in the CAP method, it is necessary to use various types of wells separately in the screening analysis that identifies allergens. At this time, a serum sample sample of 40 microliters is required for each well, and a large amount of blood sample is likely to be required. Therefore, for example, when measuring the maximum 13 items that can be performed with a normal insurance score, a serum sample of 520 microliters is required. For this reason, about 1 milliliter is required as a blood sample, which is a barrier to application to testing of infants.

  In contrast, the MAST method is a technical method developed for the purpose of improving the analysis efficiency. The MAST method is an abbreviation for Multiple Antigen Simultaneous Test, and means a simultaneous multi-item allergen-specific IgE antibody measurement method. Patent Document 1 describes a configuration related to the MAST method. In the method of Patent Document 1, a plurality of carriers bound to different allergens are arranged in a long support container, and a specimen sample is allowed to act on the entire interior of the container. Thereafter, individual carrier signal intensity is analyzed, and the amount of IgE antibody against each allergen is analyzed. With this method, up to 33 types of antigens can be analyzed simultaneously, and the serum sample is as small as 200 microliters.

By the way, in the clinical field, an opportunity to apply a clinical field immediate test, so-called point of care testing (POCT) is increasing. POCT has the advantage that a medical worker performs an inspection beside the subject or the subject himself / herself performs an inspection and obtains an inspection result on the spot. Therefore, POCT is expected to provide quick and appropriate medical care / nursing compared to the case of requesting an inspection from an external inspection organization, which improves medical quality and patient satisfaction (QOL: Quality of life). (Non-patent Document 4).
POCT is also expected for allergy diagnosis. However, the aforementioned CAP method has a problem that the analyzer is large. That is, the analyzer is installed in a specialized laboratory, and it is usual to request an examination from an external laboratory from the clinical site. In addition, in the MAST method described in Patent Document 1, the time required for measurement is 6 hours, and there is a problem that the measurement time is too long. Therefore, the CAP method and the MAST method are not suitable as methods used for POCT.

As configurations usable in POCT, configurations described in Patent Documents 2 to 4 and Non-Patent Document 5 are conventionally known.
Patent Document 2 describes a configuration related to an immunochromatography method that achieves both multi-item inspection and on-site inspection. The immunochromatography method uses a thin layer chromatography method often used in POCT. In the immunochromatography method, a thin layer in which the sample solution of the specimen is automatically developed by capillary action is used without using wells. In the thin layer, the allergen is linearly solidified in the middle of the direction in which the sample solution develops. Therefore, when the sample solution develops a thin layer, the antibody in the sample solution can react with the allergen. In the immunochromatography method, inspection can be performed by performing a step of injecting a sample solution and a color developing solution, and therefore, it is easy to make a cassette and can be used in the field.

  As another configuration in which the processing process is automated, Patent Document 3 describes a biochip automatic analysis system (1). In Patent Document 3, a well-shaped biochip (2) is used. On the biochip (2), 20 or more types of allergens are light-fixed as spots (2d). In Patent Document 3, a biochip (2) is first installed in an installation station (8), and blood serum as a sample is discharged into the biochip (2) with a manual pipette or the like. The biochip (2) from which the specimen has been discharged is automatically carried from the installation station (8) to the nozzle station (9) by the belt conveyor (14). When the biochip (2) reaches the nozzle station (9), the cleaning liquid, antibody reagent, luminescent reagent, and suction nozzles (9a to 9d) are integrally lowered from above to form the nozzles (9a to 9a). The tip of 9d) is placed inside the biochip (2).

  At this time, first, the suction nozzle (9d) is operated to suck out the sample liquid in the biochip (2). Thereafter, the cleaning liquid in the cleaning liquid tank (21) is discharged from the cleaning liquid nozzle (9a), and the inside of the biochip (2) is cleaned. The cleaning liquid after cleaning is sucked out by the suction nozzle (9d). Then, a labeled antibody, that is, an antibody reagent is injected into the biochip (2). The antibody reagent reacts only with the spot (2d) that has reacted with the specimen. When a predetermined reaction time elapses, the remaining antibody reagent is sucked out and the inside of the biochip (2) is washed again. When the washing of the antibody reagent is completed, the luminescent reagent is injected into the biochip (2). The luminescent reagent reacts only with the spot (2d) that has reacted with the antibody reagent to cause the spot (2d) to emit light. When the reagent injection process is completed, the nozzles (9a to 9d) are raised to their original positions, the belt conveyor (14) is operated, and the biochip (2) is moved from the nozzle station (9) to the CCD camera station ( 10). In the CCD camera station (10), the light emission state of the spot (2d) in the biochip (2) is imaged by the CCD camera (10c), and it is possible to specify allergens of multiple items based on the light emission intensity.

  Further, Patent Document 4 describes a biochemical reaction chip (10) that can be used in an automated processing step, a drainage processing method, and the like. The biochemical reaction chip (10) of Patent Document 4 has a square substrate (1). A cylindrical wall (2) is supported on the substrate (1). On the substrate (1), a hydrophobic ring (4) hydrophobically coated concentrically with the cylindrical wall (2) is provided inside the cylindrical wall (2). A large number of allergens are fixed as spots inside the hydrophobic ring (4). In Patent Document 4, when the cleaning liquid or the like is injected, the inside of the cylindrical wall portion (2) is filled with liquid, and the entire upper surface of the substrate (1) is filled with liquid. At the time of draining, the nozzle (31) is moved relatively to the inside of the hydrophobic ring (4) and sucked so that the entire surface of the substrate (1) is covered with the liquid. Thereafter, the nozzle (31) is moved relatively between the hydrophobic ring (4) and the cylindrical wall (2) to perform the second suction. Thereby, in patent document 4, it drains from the chip | tip for biochemical reaction (10) using the cohesive force of a liquid. Patent Document 4 describes assisting drainage by tilting the biochemical reaction chip (10) or blowing the biochemical reaction chip (10).

JP-A-60-87953 (page 3, upper left column, line 1 to page 6, upper right column, line 12, FIGS. 1 to 5) JP 2002-286716 A ("0013" to "0040", FIG. 1) Japanese Unexamined Patent Publication No. 2011-13000 (“0034” to “0041”, FIG. 3) JP 2013-24605 A (“0028” to “0035”, “0056” to “0065”, FIG. 1)

"Mechanism of allergy", [online], [Searched on December 26, 2013], Internet <URL: http://www.zaditen-al.jp/pharmacist/mechanism.html> Hayato Kubo, [online], [Search on December 26, 2013], Internet <URL: http://www.rcai.riken.jp/group/IgE/> Dermatology, "Prick Test", [online], [Search on December 26, 2013], Internet <URL: http://kompas.hosp.keio.ac.jp/contents/000358.html> Shuji Matsuo, "Current Status and Issues of POCT", [online], [Search on December 26, 2013], Internet <URL: http://plaza.umin.ac.jp/naraamt/mahoroba_vol20/P9%20wadai .htm> Y. Ito et al, Automated microfluidic assay system for autoantibodies found in autoimmune diseases using a photoimmobilized autoantigen microarray, Biotechnol.Prog. 24, American Institute of Chemical Engineers, 1384-1392 (2008).

For allergens of multiple items, there is a strong demand for high-precision judgment on the spot, and expectations for POCT are high.
However, in the immunochromatography method described in Patent Document 2 applicable to POCT, allergens that can be used at one time are set to three items or less. Further, the immunochromatography method has a problem that the detection sensitivity and accuracy are likely to be lowered. Therefore, the immunochromatography method described in Patent Document 2 has a problem that it can be used only as a very simple screening method.
In addition, the microarray chip method described in Non-Patent Document 5 has a problem that the process of injecting the reagent into the flow path on the slide substrate is complicated and the apparatus cannot be easily downsized. In Non-Patent Document 5, the inspection takes 30 minutes or more.

  Moreover, in the structure of patent document 3, 4, when discharging the liquid in a chip | tip, the liquid is sucked out from the chip | tip using a nozzle. Here, the liquid has surface tension and viscosity, and the flowability of the liquid is different. Therefore, at the time of draining, it is necessary to change the position of the nozzle and suck the inside of the chip many times, and there is a problem that it takes time and labor. Further, there is a limit in the suction force and suction range in the configuration in which the liquid is sucked by the nozzle, and there is a problem that the liquid in the chip cannot be sucked completely and the liquid remains to some extent. Therefore, in Patent Documents 3 and 4, there is a problem that reagents remaining after draining after washing affect the luminescence reaction and the like, causing background noise and lowering the determination accuracy. In addition, in the configurations of Patent Documents 3 and 4, there is a problem that the chip is not covered with a seal or the like, and foreign matter enters the chip, or the sample liquid and the reagent are easily scattered from the chip.

The first technical problem of the present invention is to improve the determination accuracy and shorten the inspection time.
Moreover, this invention makes it the 2nd technical subject to improve operativity and to improve safety | security.

In order to solve the technical problem, an inspection system according to claim 1 is provided.
A turntable rotatable around the center of rotation;
An inspection base supported by the turntable, wherein the detection target is a storage unit that can store a liquid test sample, and the detection target is disposed in the storage unit and the test sample contains a component to be detected A spot for fixing a component that reacts with the component, a drainage portion disposed radially outside the storage portion with respect to the rotation center, and a separation that separates the storage portion and the drainage portion An inspection base having a portion;
A rotational drive mechanism for rotationally driving the rotary table;
A cleaning liquid supply section for supplying a cleaning liquid to the housing section of the inspection substrate;
When the cleaning liquid is supplied via the rotational drive mechanism, the liquid is discharged from the liquid by rotating the turntable at a rotational speed at which centrifugal force is applied to move the liquid from the container to the liquid drain. Means for controlling the drainage of the cleaning liquid to be moved to the unit,
An observation member for observing the spot of the container when the cleaning liquid is drained from the container;
It is provided with.

The invention according to claim 2 is the inspection system according to claim 1,
An absorber that absorbs the liquid that has been disposed in the drainage section and has moved to the drainage section;
It is provided with.

The invention according to claim 3 is the inspection system according to claim 1 or 2,
A transparent coating member that covers the storage unit and the drainage unit from above, and a supply port that is formed in the coating member and that is supplied with a liquid test sample and cleaning liquid, and when viewed from above, The inspection base having the supply port provided at a position corresponding to the accommodating portion and non-overlapping in a spot;
The observation member disposed above the turntable;
It is characterized by providing.

The invention according to claim 4 is the inspection system according to any one of claims 1 to 3,
The separation unit having an inclined surface that is inclined upward in the direction of gravity toward the drainage unit from the storage unit, and a standing wall-like wall portion provided on the drainage unit side of the inclined surface,
It is provided with.

The invention according to claim 5 is the inspection system according to any one of claims 1 to 4,
When the cleaning liquid is supplied, the liquid is allowed to flow in the storage unit by rotating the turntable at a non-discharge rotational speed at which a centrifugal force capable of retaining the liquid in the storage unit is applied. A control means for controlling the drainage of the cleaning liquid, which rotates the rotating table at the rotational speed for discharging on which a centrifugal force that moves from the containing section to the draining section acts;
It is provided with.

The invention according to claim 6 is the inspection system according to any one of claims 1 to 5,
A second turntable that supports the inspection substrate and is rotatably supported by the turntable;
It is provided with.

The invention according to claim 7 is the inspection system according to any one of claims 1 to 4,
A vibration source that contacts the inspection substrate and applies vibration to the inspection substrate to agitate the liquid in the container;
It is provided with.

The invention according to claim 8 is the inspection system according to any one of claims 1 to 7,
The cleaning liquid supply unit and the reagent supply unit configured by a cartridge having a plurality of liquid containers in which the liquid supplied to the storage unit of the test substrate is stored in small portions;
It is provided with.

In order to solve the technical problem, an inspection method according to claim 9 comprises:
A container capable of accommodating a liquid test sample, and a spot that is disposed in the container and in which a component that reacts with the component to be detected when the test sample contains a component to be detected is fixed; The inspection substrate having a drainage part arranged adjacent to the accommodation part and a separation part for separating the accommodation part and the drainage part is provided on a turntable that can rotate around a rotation center. A step of disposing the drainage part on the outer side in the radial direction with respect to the center of rotation than the accommodating part and supporting the turntable;
Supplying an inspection sample to the inspection substrate;
Supplying a cleaning liquid to the housing portion of the inspection substrate;
When the cleaning liquid is supplied, the liquid discharging step of moving the liquid to the liquid discharging part by rotating the turntable at a rotational speed at which centrifugal force is applied to move the liquid from the containing part to the liquid discharging part. When,
A step of observing the spot of the container when the cleaning liquid is drained from the container;
It is characterized by performing.

In order to solve the technical problem, an inspection substrate according to claim 10 is provided.
A rotating table that is rotatable about the rotation center and rotated when the liquid is drained, a supply unit that supplies the cleaning liquid, an observation member that is observed when the liquid test sample and the cleaning liquid are drained, An inspection substrate used in an inspection apparatus and supported by the turntable,
A container capable of accommodating a liquid test sample;
A spot in which a component that reacts with the component to be detected is fixed when the component to be detected is included in the test sample,
A drainage part that is disposed radially outside the storage part with respect to the rotation center of the turntable, and that drains liquid from the storage part when the turntable rotates;
A separation unit that separates the storage unit and the drainage unit;
It is provided with.

According to the first, ninth, and tenth aspects of the present invention, the determination accuracy can be improved and the inspection time can be shortened compared to the case where the centrifugal force is applied and the liquid is not drained.
According to invention of Claim 2, compared with the case where an absorber is not arrange | positioned, it can reduce that a liquid flows out, can improve operativity, and can improve safety | security.
According to invention of Claim 3, operativity can be improved compared with the case where it does not have a coating | coated member, and safety | security can be improved. Furthermore, it is possible to suppress the supply port from adversely affecting spot observation, and the determination accuracy can be improved.

According to the fourth aspect of the present invention, compared with the case where the configuration of the present invention is not provided, it is possible to prevent the liquid once drained from returning to the storage unit again while making it easier to hold the liquid in the storage unit. . As a result, the determination accuracy can be improved.
According to the fifth aspect of the present invention, compared with the case where the cleaning liquid does not flow in the storage section, the liquid in the storage section can be easily mixed with the cleaning liquid and discharged together with the cleaning liquid.
According to the sixth aspect of the present invention, it is possible to suppress the deviation of the centrifugal force acting on the inspection substrate, and the liquid can be appropriately stirred.

According to invention of Claim 7, compared with the case where it stirs with a centrifugal force, a liquid can be stirred in a short time.
According to invention of Claim 8, a structure can be simplified compared with the case where a liquid is supplied using a nozzle and a pump.

FIG. 1 is an overall explanatory diagram of a diagnostic system according to a first embodiment of the present invention. FIG. 1A is an explanatory diagram when the rotating station is moved to an observation position, and FIG. 1B is an explanatory diagram when the rotating station is moved to a cleaning liquid position. It is. FIG. 2 is an explanatory diagram of the rotating station according to the first embodiment of the present invention, and is an explanatory diagram when the rotating station moves to the zero point position. FIG. 3 is an explanatory diagram of the positioning sensor. 4 is an explanatory diagram of the chip cassette according to the first embodiment of the present invention, FIG. 4A is a plan view, and FIG. 4B is a sectional view taken along line IVB-IVB in FIG. 4A. FIG. 5 is an explanatory diagram showing the functions of the personal computer according to the first embodiment of the present invention in a block diagram (functional block diagram). FIG. 6 is a flowchart of the reaction observation process according to the first embodiment of the present invention. FIG. 7 is a flowchart of the reaction rotation process according to the first embodiment of the present invention, which is a subroutine of ST2 in FIG. FIG. 8 is a flowchart of the cleaning process according to the first embodiment of the present invention, and is a subroutine of ST3 and ST5 of FIG. FIG. 9 is a flowchart of the cleaning drainage process according to the first embodiment of the present invention, which is a subroutine of ST206 in FIG. FIG. 10 is a flowchart of the antibody reagent process of Example 1 of the present invention, which is a subroutine of ST4 in FIG. FIG. 11 is a flowchart of the reaction rotation process of the antibody reagent of Example 1 of the present invention, which is a subroutine of ST405 in FIG. FIG. 12 is a flowchart of the luminescent reagent process according to the first embodiment of the present invention, which is a subroutine of ST6 in FIG. FIG. 13 is a flowchart of the imaging process according to the first embodiment of the present invention, which is a subroutine of ST7 in FIG. FIG. 14 is a flowchart of end processing according to the first embodiment of the present invention, which is a subroutine of ST8 of FIG. FIG. 15 is a flowchart of the end drainage process according to the first embodiment of the present invention, which is a subroutine of ST701 in FIG. FIG. 16 is an operation explanatory diagram of Embodiment 1 of the present invention, FIG. 16A is an explanatory diagram of a state in which a liquid is supplied to the reaction area, FIG. 16B is an explanatory diagram of a state in which a cleaning liquid is supplied to FIG. 16C is an explanatory diagram when rotating at a medium speed from FIG. 16B, and FIG. 16D is an explanatory diagram when rotating at a high speed from FIG. 16C. FIG. 17 is an explanatory diagram of the experimental results of Experimental Example 1. FIG. 18 is an explanatory diagram of experimental results of Experimental Example 2 and Comparative Example 1. 19 is an explanatory diagram of the experiment of Experimental Example 3, FIG. 19A is an explanatory diagram of spot allergens, FIG. 19B is an explanatory diagram of observation results of the first specimen liquid, and FIG. 19C is an observation result of the second specimen liquid. FIG. 19D is an explanatory diagram of the observation result of the third specimen liquid. 20 is an explanatory diagram of the observation result of Experimental Example 4, FIG. 20A is a diagram showing the relationship between the signal intensity of the standard sample solution and the CAP value, FIG. 20B is an enlarged view of the main part of the portion with a small CAP value in FIG. FIG. 20C is a diagram showing the relationship between signal intensity and CAP value when measuring mite allergen. FIG. 21 is an explanatory diagram of Experimental Example 6, FIG. 21A is an explanatory diagram of spot arrangement positions, and FIG. 21B is an explanatory diagram of observation results of a chip cassette. 22 is an explanatory view of a chip cassette according to the second embodiment of the present invention, FIG. 22A is a plan view corresponding to FIG. 4A of the first embodiment, and FIG. 22B is a sectional view taken along the line XXIIB-XXIIB in FIG. It is a figure corresponding to FIG. 4B of Example 1. FIG. FIG. 23 is an explanatory diagram of the main part of the diagnostic system of Example 3 of the present invention, FIG. 23A is an explanatory diagram of the rotating station, FIG. 23B is a case where the rotating station is moved to the zero point position and the rotating unit is moved to the reference position FIG. 23C is an explanatory view of a coil spring on the rotation station of FIG. 23B. FIG. 24 is an explanatory diagram of a main part of the diagnostic system according to the fourth embodiment of the present invention.

Next, specific examples of embodiments of the present invention (hereinafter referred to as examples) will be described with reference to the drawings, but the present invention is not limited to the following examples.
In order to facilitate understanding of the following description, in the drawings, the front-rear direction is the X-axis direction, the left-right direction is the Y-axis direction, the up-down direction is the Z-axis direction, and arrows X, -X, Y, -Y, The direction indicated by Z and -Z or the indicated side is defined as the front side, the rear side, the right side, the left side, the upper side, the lower side, or the front side, the rear side, the right side, the left side, the upper side, and the lower side, respectively.
In the figure, “•” in “○” means an arrow heading from the back of the page to the front, and “×” in “○” is the front of the page. It means an arrow pointing from the back to the back.
In the following description using the drawings, illustrations other than members necessary for the description are omitted as appropriate for easy understanding.

FIG. 1 is an overall explanatory diagram of a diagnostic system according to a first embodiment of the present invention. FIG. 1A is an explanatory diagram when the rotating station is moved to an observation position, and FIG. 1B is an explanatory diagram when the rotating station is moved to a cleaning liquid position. It is.
FIG. 2 is an explanatory diagram of the rotating station according to the first embodiment of the present invention, and is an explanatory diagram when the rotating station moves to the zero point position.

(Description of diagnostic device S1)
(Description of rotating station 1)
As an example of the inspection apparatus, a diagnostic apparatus S1 that can be used for diagnosis of an allergy test includes a rotation station 1 as an example of a turntable. The rotation station 1 is formed in a disk shape having a thickness in the vertical direction. On the upper surface of the rotation station 1, a set unit 2 as an example of an installation unit is formed. The set portion 2 is formed at a position spaced radially from the central portion 1a of the disk of the rotary station 1. The set portion 2 is formed in a concave shape corresponding to a chip cassette S2 as an example of an inspection substrate. A chip cassette S2 is detachably supported by the set unit 2.

  The central portion 1a of the rotary station 1 is supported by a rotary shaft 3 that is oriented in the vertical direction. That is, the longitudinal direction of the rotating shaft 3 is along the vertical direction. The lower end of the rotary shaft 3 is an example of a first drive mechanism, and is rotatably supported by a rotary mechanism 4 as an example of a rotary drive mechanism. Driving is transmitted to the rotating shaft 3 from a stepping motor 6 as an example of a driving source of the rotating mechanism 4. The stepping motor 6 is an example of an information processing device, and is electrically connected to a personal computer PC as an example of a control device, and the drive is controlled by the personal computer PC. Therefore, the rotation station 1 is rotated by driving the stepping motor 6.

FIG. 3 is an explanatory diagram of the positioning sensor.
1 and 3, a positioning sensor 11 as an example of an initial position detection member is disposed on the left side of the rotation station 1. The positioning sensor 11 detects a detected part 12 provided in the rotation station 1. The detected part 12 is arranged corresponding to the case where the set part 2 on the rotating station 1 moves to a zero point position P1 as an example of the initial position shown in FIGS. That is, when the rotary station 1 moves to the zero point position P1, the detected part 12 is arranged at a position where the sensor 11 detects the detected part 12. The positioning sensor 11 and the detected part 12 constitute a position detection mechanism 13 according to the first embodiment.
The rotational movement of the rotary station 1 is controlled with reference to the zero point position P1. In FIG. 2, the rotation station 1 corresponds to each of the positions P2 to P5 corresponding to the case where the set unit 2 moves to the observation position P2, the cleaning liquid position P3, the antibody reagent position P4, and the luminescent reagent position P5 set in advance. The rotation is performed based on the zero point position P1 by a preset rotation angle.

(Description of nozzle device 21)
1 and 2, a nozzle device 21 as an example of a supply device is disposed above the rotation station 1. The nozzle device 21 includes nozzles 22, 23, and 24 as an example of a supply unit. Each nozzle 22-24 is arrange | positioned on the same periphery centering on the rotating shaft 3. FIG. In FIG. 2, a cleaning liquid nozzle 22 as an example of a cleaning liquid supply unit is disposed on the right front side corresponding to the cleaning liquid position P3. The nozzle 23 of the antibody reagent container as an example of the antibody reagent supply unit is arranged on the right rear side corresponding to the antibody reagent position P4. Furthermore, the nozzle 24 of the luminescent reagent container as an example of the luminescent reagent supply unit is arranged on the left rear side corresponding to the luminescent reagent position P5.

  In FIG. 1B, the nozzles 22 to 24 are supported by the support member 26. The support member 26 is supported by a nozzle lifting mechanism 27 as an example of a second drive mechanism so as to be movable up and down. Therefore, each nozzle 22-24 is comprised so that raising / lowering together with the supporting member 26 is possible. Accordingly, each of the nozzles 22 to 24 is configured to be movable between an injection position shown in FIG. 1B as an example of a lowered position and a retracted position (not shown) as an example of a raised position. Drive is transmitted to the support member 26 from a stepping motor 28 of an elevating mechanism 27. The stepping motor 28 is electrically connected to a personal computer PC, and the drive is controlled by the personal computer PC.

  In FIG. 1B, the cleaning liquid nozzle 22 has a discharge port 22a formed at the lower end and a supply port 22b formed at the upper end. One end of a tube 29 as an example of a tube is connected to the supply port 22b. The other end of the tube 29 is connected to a tank 31 as an example of a storage unit. The tank 31 stores a cleaning liquid L1. The tank 31 is connected to a pump 32 as an example of a supply drive source. A personal computer PC is electrically connected to the pump 32, and the driving of the pump 32 is controlled by the personal computer PC. Therefore, the cleaning liquid nozzle 22 can be supplied with the cleaning liquid L <b> 1 from the tank 31 via the tube 29. That is, the cleaning liquid L1 can be supplied and injected into the chip cassette S2 from the discharge port 22a of the cleaning liquid nozzle 22.

  Further, a liquid antibody reagent L2 can be supplied and injected into the chip cassette S2 from the nozzle 23 of the antibody reagent container. Further, a liquid luminescent reagent L3 can be supplied and injected into the chip cassette S2 from the nozzle 24 of the luminescent reagent container. The configuration in which the antibody reagent L2 is supplied to the nozzle 23 of the antibody reagent container and supplied into the chip cassette S2 or the configuration in which the luminescent reagent L3 is supplied to the nozzle 24 of the luminescent reagent container and supplied into the chip cassette S2 is supplied to the cleaning liquid nozzle 22. The cleaning liquid L1 is configured in the same manner as the structure for supplying it into the chip cassette S2. Therefore, the detailed description about the structure which supplies reagent L2, L3 from the nozzle 23 of an antibody reagent container and the nozzle 24 of a luminescent reagent container is abbreviate | omitted.

  Here, in the tank 31 'of the nozzle 23 of the antibody reagent container of Example 1, as an example of the antibody reagent, a reagent solution for labeling of anti-IgE antibody added with horseradish peroxidase (HRP) as a labeling agent is provided. It is stored. In addition, in the tank 31 ″ of the nozzle 24 of the luminescent reagent container of Example 1, a luminescent reagent solution obtained by mixing a reagent solution containing hydrogen peroxide and a reagent solution containing luminol is stored as an example of the luminescent reagent. As the luminescent reagent, a one-component reagent such as alkaline phosphatase can also be used.

  In Example 1, the antibody reagent L2 and the luminescent reagent L3 are stored in the tanks 31 ′ and 31 ″ and the reagents L2 and L3 are supplied from the tanks 31 ′ and 31 ″. However, the present invention is not limited to this. . For example, a configuration using a reagent container as an example of a container filled with a reagent is possible. The reagent container is filled with a reagent that is easily denatured and difficult to store, and is used up once to improve convenience. In other words, the nozzles 23 and 24 may be configured such that the reagent containers are replaced and mounted for each chip cassette S2 instead of the tubes 29 'and 29 "and the tanks 31' and 31". At this time, a configuration in which the reagent container itself has the functions of the nozzles 23 and 24 is also possible.

(Description of camera device 41)
1 and 2, a camera device 41 as an example of an observation device is arranged above the left portion of the rotation station 1 in correspondence with the observation position P2. The camera device 41 is an example of a support member, and includes a frame 42 as an example of a frame body. The frame 42 supports a camera 43 as an example of an observation member and an example of a main body of the observation apparatus. The camera 43 includes a lens 44 as an example of an optical system and a CCD 46 as an example of an imaging device that receives light that has passed through the lens 44. The CCD 46 is electrically connected to a personal computer PC. That is, the image captured by the CCD 46 is transmitted to the personal computer PC.

  A camera hood 47 as an example of a dark box member is disposed outside the camera 43 in the front-rear and left-right directions. The camera hood 47 is configured in a cylindrical shape extending in the up-down direction, and the inner periphery of the cross section is configured to be larger than the outer periphery of the set unit 2. The camera hood 47 is supported so as to be movable in the vertical direction along a guide portion 48 provided on the frame 42. The camera hood 47 supports a rack portion 49 extending in the vertical direction as an example of a transmitted portion. The rack portion 49 is engaged with a gear 51 as an example of a transmission portion. The gear 51 is supported on a drive shaft 52 a of a motor 52. The motor 52 is configured to be rotatable forward and backward. The motor 52 is electrically connected to the personal computer PC, and the drive is controlled by the personal computer PC.

Therefore, when the motor 52 is driven in the forward and reverse directions, the camera hood 47 is transmitted through the gear 51 and the rack portion 49, and the covering position shown in FIG. 1A as an example of the dark box lowering position and the dark box rising position. It moves between the open positions shown in FIG. 1B as an example. In the first embodiment, when the camera hood 47 moves to the covering position, the lower end contacts the upper surface of the rotation station 1. At this time, the camera hood 47 shields the light from entering the camera 43 from the outside.
The guide portion 48, the rack portion 49, the gear 51, and the motor 52 constitute a hood lifting mechanism 53 as an example of a third drive mechanism of the first embodiment. The frame 42, the camera 43, the camera hood 47, and the hood lifting / lowering mechanism 53 constitute the camera device 41 of the first embodiment.

(Description of temperature control mechanism 61)
In FIG. 1, a temperature control mechanism 61 is disposed below the rotation station 1. The temperature control mechanism 61 includes a disc 62 as an example of a support member. The disk 62 is fixedly disposed in the vicinity of the lower surface of the rotation station 1. A microheater 63 as an example of a temperature raising member is supported on the upper surface of the disc 62. The micro heater 63 raises the temperature of the lower surface of the rotation station 1 and the chip cassette S2. The temperature control mechanism 61 includes a temperature sensor 64 as an example of an environmental temperature detection member. The temperature control mechanism 61 of Example 1 is electrically connected to the personal computer PC, and controls the micro heater 63 based on the detected temperature. The temperature control mechanism 61 according to the first embodiment holds the lower surface of the rotation station 1 and the chip cassette S2 at a preset temperature. In the first embodiment, the temperature is held at 38 degrees as an example.
The rotation station 1, the rotation mechanism 4, the position detection mechanism 13, the nozzle device 21, the camera device 41, the temperature control mechanism 61, and the like constitute the diagnosis device S1 of the first embodiment. Further, a diagnostic system S as an example of the inspection system of the first embodiment is configured by the diagnostic device S1, the chip cassette S2, the personal computer PC, and the like.

(Description of chip cassette S2)
4 is an explanatory diagram of the chip cassette according to the first embodiment of the present invention, FIG. 4A is a plan view, and FIG. 4B is a sectional view taken along line IVB-IVB in FIG. 4A.
In FIG. 4, a chip cassette S <b> 2 as an example of an inspection substrate has a flat substrate 101. The substrate 101 is formed in a square shape. On the upper surface 101a of the substrate 101, a hydrophobic ring 102, which is an example of a separation portion and an example of a hydrophobic portion, is formed. The hydrophobic ring 102 is formed in an annular shape having a preset width. The hydrophobic ring 102 is hydrophobized and has a higher hydrophobicity than the other upper surface 101a. In the first embodiment, the hydrophobic ring 102 is configured by applying a hydrophobic material in an annular shape on the upper surface 101a. In addition, the structure of such a hydrophobic ring 102 is conventionally well-known, For example, the structure of Unexamined-Japanese-Patent No. 2013-24605 is applicable. Therefore, detailed description of the hydrophobic ring 102 is omitted.

  In FIG. 4A, the upper surface 101 a of the substrate 101 is separated into an inner region and an outer region by a hydrophobic ring 102. A region inside the hydrophobic ring 102 constitutes a reaction area A1 which is an example of a storage unit and an example of a reaction region. In addition, the area outside the hydrophobic ring 102 constitutes a drainage area A2 which is an example of a drainage part and an example of a drainage area. In other words, the drainage area A2 of Example 1 has a region arranged on the outer side in the radial direction than the reaction area A1 with respect to the rotation center 3. The reaction area A1 and the drainage area A2 are adjacent to each other with the hydrophobic ring 102 interposed therebetween.

  In the reaction area A1, a plurality of spots 103 to which components that react with the detection target component are fixed when the liquid test sample includes the detection target component are arranged. The spots 103 are arranged on the upper surface 101a of the substrate 101 with a predetermined interval in a predetermined direction. In the first embodiment, in FIG. 4A, two rows are arranged in the front-rear direction and four rows are arranged in the left-right direction, and a total of eight spots 103 are arranged. Here, the diagnosis system S of the first embodiment is configured to be able to diagnose an allergy test. Therefore, in Example 1, a test sample that can contain an antibody as a component to be detected is used as an example of a liquid test sample. Specifically, the sample liquid L0 based on blood collected from the subject is used. As the sample liquid L0, any of whole blood, serum, and plasma can be used, and those diluted with a buffer can also be used as the sample liquid L0. In addition, a large amount of an antigen, which is a component that reacts with an antibody, is additionally immobilized on the spot 103 in the spot 103 of Example 1. In Example 1, an allergen extract or a recombinant allergen is fixed to the spot 103 as an example of an antigen. Note that the number and arrangement of the spots 103 are not limited to the above-described configuration, and an arbitrary number and arrangement are possible. In addition, the number of spots 103 is desirably eight or more from the viewpoint of simultaneous inspection of multiple items.

A cassette retaining wall 104 as an example of a side wall portion of the base is supported in the drainage area A2. The cassette retaining wall 104 has an outer wall portion 106 formed in a square tube shape along the outer periphery of the substrate 101. The outer wall portion 106 extends upward. A square plate-like upper bottom portion 107 is supported on the upper end 106 a of the outer wall portion 106. In FIG. 4A, a circular hole 107 a concentric with the hydrophobic ring 102 and larger than the hydrophobic ring 102 is formed in the upper bottom portion 107. The upper bottom 107 supports a cylindrical inner wall 108 extending downward from the inner periphery of the hole 107a. The lower end 108a of the inner wall portion 108 is separated from the substrate 101 with a predetermined interval.
The outer wall portion 106, the upper bottom portion 107, and the inner wall portion 108 constitute the cassette retaining wall 104 of the first embodiment.

  In FIG. 4B, a holding space 109 according to the first embodiment is configured by a space surrounded by the substrate 101, the outer wall portion 106, the upper bottom portion 107, and the inner wall portion 108. Further, the water absorption groove 111 according to the first embodiment is configured by the gap between the inner wall portion 108 and the substrate 101. Therefore, the holding space 109 is spatially connected to the drainage area A <b> 2 via the water absorption groove 111. In the holding space 109, a water absorbent 112 as an example of an absorber is accommodated. The water absorbing agent 112 absorbs the liquid that has moved to the water absorbing groove 111. As the water absorbing agent 112, for example, silica gel can be used. Further, the absorbent body is not limited to a drug such as a water-absorbing agent, and a liquid-absorbable member such as Japanese Pharmacopoeia absorbent cotton can also be used.

A square plate-like seal 113 as an example of a covering member is supported on the upper surface 107 b of the cassette retaining wall 104. The seal 113 is made of a transparent member. Therefore, when the upper surface 101 a is observed from above, the spot 103 of the substrate 101 can be observed through the seal 113. An injection hole 113a as an example of a supply port is formed in the seal 113 corresponding to the reaction area A1. In FIG. 4A, when viewed from above, in Example 1, the injection hole 113a is formed at a position that does not overlap with the spot 103. Further, an identification seal (not shown) as an example of an identification display member is attached to the upper surface of the seal 113 so as to correspond to a position that does not overlap with the reaction area A1 and can be imaged by the camera 43. A bar code as an example of an identifier is displayed on the identification seal, and is imaged together with the spot 103 by the camera 43. Therefore, in the first embodiment, the barcode is read by the camera 43. The barcode is used for one-to-one correspondence between the subject and the chip cassette S2. As the identifier, a two-dimensional code, character information, or the like can be used instead of the one-dimensional barcode.
The chip cassette S2 of Example 1 is configured by the substrate 101, the hydrophobic ring 102, the spot 103, the cassette retaining wall 104, the water absorbing agent 112, the seal 113, and the like.

  It should be noted that the substrate 101 and the seal 113 of the chip cassette S2 are made of a material having optically excellent characteristics that has no birefringence and does not absorb light in the visible light region. In particular, the substrate 101 is preferably a glass substrate, a silicon substrate, or a plastic substrate that has been surface-treated for protein immobilization. Among these substrates, a substrate fixed with a light fixing polymer is particularly desirable. Note that the light-fixing polymer-coated substrate is described in International Publication No. 2009/119082, and thus detailed description thereof is omitted.

(Description of PC)
FIG. 5 is an explanatory diagram showing the functions of the personal computer according to the first embodiment of the present invention in a block diagram (functional block diagram).
In FIG. 5, the personal computer PC of the first embodiment is configured by a so-called computer device, which is an example of a computer main body H1, a display, a touch panel H2 as an example of an input unit, and a nonvolatile semiconductor (not shown). It is comprised by memory, what is called flash memory.

The computer main body H1 of the personal computer PC stores I / O (input / output interface) for input / output of signals to / from the outside and adjustment of input / output signal level, programs and data for performing necessary startup processing, and the like. ROM (Read Only Memory), RAM (Random Access Memory) for temporarily storing necessary data and programs, CPU (Central Processing Unit) for performing processing according to the startup program stored in ROM, etc., and A clock oscillator or the like is included, and various functions can be realized by executing programs stored in the ROM and RAM.
The personal computer PC having the above configuration can realize various functions by executing a program stored in the flash memory, ROM, or the like.
In the computer main body H1, basic software for controlling basic operations, so-called operating system OS, reaction observation program as an application program, and other software (not shown) are stored in a hard disk drive (HDD), a solid state drive (SSD), or the like. Has been.
The computer main body H1 has a communication function and is configured to be able to transmit and receive information to and from other information processing apparatuses via a communication line.

(Signal output element connected to computer main body H1)
The computer main body H1 receives the output signals of the following signal output elements H2, 11, 46 and 64.
H2: Touch panel The touch panel H2 detects an input to the touch panel H2, and inputs the detection signal to the computer main body H1.
11: Positioning sensor The positioning sensor 11 inputs a detection signal indicating whether or not the rotation station 1 has moved to the zero point position P1 to the computer main body H1.
46: CCD
The CCD 46 inputs the captured image signal to the computer main body H1.
64: Temperature sensor The temperature sensor 64 inputs the environmental temperature to the computer main body H1.

(Controlled element connected to computer main body H1)
The computer main body H1 outputs control signals for the following controlled elements H2, D1 to D7.
H2: Touch panel The touch panel H2 displays an image based on the image signal transmitted from the computer main body H1.
D1: Rotation Drive Circuit The rotation drive circuit D1 as an example of the first drive circuit drives the stepping motor 6 of the rotation mechanism 4 to rotate the rotation station 1.
D2: Nozzle Lift Circuit A nozzle lift circuit D2 as an example of a second drive circuit drives the stepping motor 28 of the nozzle lift mechanism 27 forward and backward to raise and lower the nozzles 22-24.
D3: Hood Lifting Circuit The hood lifting circuit D3 as an example of the third drive circuit drives the stepping motor 52 of the hood lifting mechanism 53 forward and backward to raise and lower the camera hood 47.

D4: Cleaning Pump Drive Circuit The cleaning pump drive circuit D4 as an example of the first supply driving source driving circuit drives the pump 32 to discharge the cleaning liquid L1 from the cleaning liquid nozzle 22.
D5: Antibody Pump Drive Circuit The antibody pump drive circuit D5 as an example of the second supply drive source drive circuit drives the pump 32 'to discharge the antibody reagent L2 from the nozzle 23 of the antibody reagent container. .
D6: Luminescent Pump Drive Circuit The luminescent pump drive circuit D6 as an example of the third supply drive source drive circuit drives the pump 32 ″ to discharge the luminescent reagent L3 from the nozzle 24 of the luminescent reagent container. .
D7: Temperature Control Circuit The temperature control circuit D7 operates the micro heater 63 and detects the environmental temperature by the temperature sensor 64.

(Function of computer main unit H1)
The computer main body H1 has a reaction observation program for controlling the operations of the controlled elements H2, D1 to D7, etc. according to the output signals of the signal output elements H2, 11, 46, 64, and the like.

(Reaction Observation Program AP1 of Example 1)
The reaction observation program AP1 as an example of the inspection program has the following functional means (program module).

C1: Reaction Rotation Unit The reaction rotation unit C1, which is an example of the first control unit of the turntable and is an example of the rotation unit having the first rotation number, rotates the rotation station 1 via the rotation drive circuit D1. Let The reaction rotating means C1 rotates the rotating station 1 at a non-discharge rotational speed N1 on which a centrifugal force capable of retaining a liquid in the reaction area A1 acts. The reaction rotation means C1 rotates the rotation station 1 at a preset first rotation speed N1 as an example of a non-discharge rotation speed. When rotating based on the input from the input unit H2 of the personal computer PC, the reaction rotating means C1 of the first embodiment rotates the rotating station 1 for a preset time T0 for reaction of the sample liquid. In addition, when rotating the antibody reagent L2 when the antibody reagent L2 is injected, the reaction rotating means C1 of Example 1 rotates the rotating station 1 for a preset time T0 ′ for the reaction of the antibody reagent. The rotational speed N1 and the times T0 and T0 ′ are set in advance based on experiments and the like. In Example 1, the time T0 for reaction of the sample liquid is set to 8 minutes as an example. As an example, the reaction time T0 ′ for the antibody reagent is set to 4 minutes.

  In the first embodiment, the configuration using the single rotation speed N1 as the rotation speed for non-discharge is exemplified, but the present invention is not limited to this. For example, a rotation that is a threshold value between a rotation speed at which a centrifugal force capable of retaining the liquid in the reaction area A1 and a discharge rotation speed at which the centrifugal force at which the liquid moves from the reaction area A1 to the drainage area A2 acts. For the number N11, the non-discharge rotational speeds N1 ′ and N1 ″ are set as rotational speeds satisfying 0 <N1 ′ <N1 ″ <Na. Then, within the reaction time T0, T0 ′, the rotation speed is first rotated at a small non-discharge rotational speed N1 ′, and when a preset time has elapsed, the non-discharge high rotational speed N1 ″ is changed. In contrast, it is possible to change from N1 ″ to N1 ′ for rotation. Further, it is possible to adopt a configuration in which the rotation speed is changed stepwise from 0 to Na within the reaction times T0 and T0 ′. In other words, the reaction rotation means C1 can be controlled by changing the rotation speed using a plurality of non-discharge rotation speeds within the reaction times T0 and T0 ′.

  Further, when the reaction rotation means C1 uses a plurality of non-discharge rotation speeds to vary the rotation speed, the rotation direction is not limited to a fixed direction, and a configuration in which the rotation direction is reversed is also possible. . That is, as a configuration in which the stepping motor 6 can be rotated forward and backward, a configuration in which the reaction rotating means C1 rotates while switching the rotation direction at a preset appropriate time is also possible. Therefore, for example, when the time T0 for reaction of the sample liquid is 8 minutes, the rotation direction is switched every 2 minutes, the first 2 minutes are rotated at the rotation speed N1, and the next 2 minutes are rotated. It is also possible to adopt a configuration in which the reverse rotation of the number N1, the next two minutes is forward rotation of the rotation number N1, and the last two minutes are reverse rotation of the rotation number N1. Similarly, for example, when the time T0 ′ for the reaction of the antibody reagent is 4 minutes, the rotation direction is changed every 1 minute, the first minute is the forward rotation of the rotation number N1, the next one minute Further, a reverse rotation of the rotation speed N1, a forward rotation of the rotation speed N1 for the next one minute, and a reverse rotation of the rotation speed N1 for the last one minute are possible. In addition, the structure which repeats rotation speed N1-N1 "for non-discharge | discharging, and the rotation speed 0, ie, the structure which repeats rotation and a stop, etc. are possible.

  Further, the time for the reaction rotating means C1 to rotate using the respective non-discharge rotation speeds is not limited to the configuration in which the reaction times T0 and T0 ′ are equally divided. For example, when the reaction time T0 is set to 8 minutes and the rotation speeds N1 ′ and N1 ″ are used as the non-discharge rotation speed, the rotation speed is N1 ′ for 4 minutes and N1 ″ for 4 minutes. Of course, it is possible to rotate it for a total of 8 minutes. Further, it is possible to change the rotation of N1 ′ and N1 ″ every 2 minutes, or change it every 30 seconds and rotate it for 4 minutes, for a total of 8 minutes. In place of these, it is possible to rotate N1 ′ for 6 minutes and N1 ″ for 2 minutes to rotate for a total of 8 minutes. In addition, it is possible to rotate at N1 ′ for 4 minutes, then at N1 ″ for 1 minute, and finally at N1 ′ for 3 minutes to rotate for a total of 8 minutes. When C1 is controlled by changing the rotation speed using a plurality of non-discharge rotation speeds, the order of the rotation speeds and the rotation direction so that the reaction times T0 and T0 ′ are obtained as a whole. The rotation speed can be made variable by arbitrarily assigning the rotation time.

C2: Cleaning Drain Rotating Means An example of the cleaning liquid drain controlling means. The cleaning drain rotating means C2 as an example of the second control means of the turntable includes the low speed rotating means C2A and the medium speed rotating. Means C2B and high-speed rotation means C2C are provided. The cleaning drainage rotation means C2 rotates the rotation station 1 via a rotation drive circuit D1. When the cleaning liquid L1 is supplied, the cleaning drain liquid rotating means C2 rotates the rotating station 1 at a non-discharge rotational speed N1 at which a centrifugal force capable of retaining the liquid in the reaction area A1 acts. The liquid is caused to flow in the reaction area A1. Further, the cleaning drainage rotation means C2 is rotated at the non-discharge rotation speed N1, and then the discharge rotation speeds N2 and N3 on which the centrifugal force that moves the liquid from the reaction area A1 to the drainage area A2 acts. Rotate the rotating station 1 to drain the liquid.

C2A: Low-speed rotation means Low-speed rotation means C2A as an example of the rotation means of the first rotation speed is a first rotation speed N1 similar to the reaction rotation means C1 as an example of the non-discharge rotation speed. Rotate 1 The low-speed rotation means C2A of the first embodiment rotates the rotation station 1 for a preset low-speed time T1 when the cleaning liquid L1 is injected into the chip cassette S2 and the nozzle 22 moves to the retracted position. The rotation speed N1 and the time T1 are set in advance based on experiments and the like. In addition, although the low-speed rotation means C2A of Example 1 illustrated the structure rotated at low speed using the single rotation speed N1, it is not limited to this. For example, similarly to the reaction rotation means C1, the low speed rotation means C2A is controlled by changing the rotation speed of the low speed rotation, for example, using a plurality of rotation speeds from 0 to the rotation speed Na within the time T1. It is also possible. Further, at this time, the low-speed rotation means C2A makes the rotation speed of the low-speed rotation variable by arbitrarily assigning the order of the rotation speed, the rotation direction, and the rotation time so that the whole time becomes the low-speed time T1. Is possible.

C2B: Medium-speed rotation means The medium-speed rotation means C2B as an example of the rotation means of the second rotation speed is a preset second speed larger than the first rotation speed N1 as an example of the rotation speed for discharge. The rotation station 1 is rotated at the rotation speed N2. The medium speed rotation means C2B of the first embodiment rotates the rotation station 1 during a preset medium speed time T2. The medium speed rotation means C2B of the first embodiment rotates the rotation station 1 when the control of the low speed rotation means C2A is completed. The rotation speed N2 and time T2 are set in advance based on experiments and the like. In addition, although the medium-speed rotation means C2B of Example 1 illustrated the structure rotated at medium speed using the single rotation speed N2, it is not limited to this. For example, similarly to the reaction rotation means C1, the medium speed rotation means C2B includes a plurality of rotation speeds Na from the low speed and medium speed threshold values to the medium speed and high speed threshold speeds Nb within the time T2. It is also possible to control by changing the rotation speed of the medium speed rotation such as using the rotation speed. At this time, the medium-speed rotation means C2B can change the rotation speed of the medium-speed rotation by arbitrarily assigning the order of the rotation speed, the rotation direction, and the rotation time so that the medium-speed time T2 is obtained as a whole. It is possible to

C2C: High-speed rotation means The high-speed rotation means C2C as an example of the rotation means of the third rotation speed is a preset third rotation speed larger than the second rotation speed N2 as an example of the discharge rotation speed. At N3, the rotation station 1 is rotated. The high-speed rotation means C2C according to the first embodiment rotates the rotation station 1 for a preset high-speed time T3. The high speed rotating means C2C of the first embodiment rotates the rotating station 1 when the control of the medium speed rotating means C2B is completed. The rotation speed N3 and the time T3 are set in advance based on experiments and the like. In addition, although the high-speed rotation means C2C of Example 1 illustrated the structure rotated at high speed using the single rotation speed N3, it is not limited to this. For example, similarly to the reaction rotation means C1, the high speed rotation means C2C makes the rotation speed of the high speed rotation variable by using a plurality of rotation speeds larger than the rotation speed Nb of the medium speed and the high speed threshold within the time T3. Can also be controlled. At this time, the high-speed rotation means C2C makes the rotation speed of the high-speed rotation variable by arbitrarily assigning the order of the rotation speed, the rotation direction, and the rotation time so that the entire high-speed time T3 is obtained. Is possible.

C3: End Drain Rotating Means An example of the luminescent reagent drain control means, and the end drain rotating means C3 as an example of the third control means of the turntable includes a high speed rotating means C3A. The end drainage rotation means C3 is used for discharging the centrifugal force that moves the luminescent reagent L3 from the reaction area A1 to the drainage area A2 when the observation of the camera 43 is completed via the rotation drive circuit D1. The rotation station 1 is rotated at the rotation speed N3, and the luminescent reagent L3 is moved to the drainage area A2.
C3A: High-speed rotation means The high-speed rotation means C3A is the high-speed rotation of the cleaning liquid rotation means C2 except that the rotation station 1 is rotated when the observation of the camera 43 is completed and the camera hood 47 is moved to the open position. The configuration is the same as that of the rotating means C2C. Therefore, the detailed description regarding the high-speed rotation means C3A is omitted.

C4: Position Control Means Position control means C4 as an example of the fourth control means of the turntable rotates the rotation station 1 via the rotation drive circuit D1 to move the rotation station 1 to positions P1 to P5. In the first embodiment, when the rotation station 1 is moved to the zero point position P1, the position control unit C4 rotates the positioning station 11 until it is detected that the rotation station 1 has moved to the zero point position P1. Further, when moving to the positions P2 to P5, a pulse is input to the stepping motor 6 by the rotation angle corresponding to each position P2 to P5 with reference to the zero point position P1, and the rotation station 1 is rotated. Thereby, the position control means C4 of Example 1 moves the rotation station 1 to each position P1-P5.

  Here, in Example 1, the position control means C4 moves the rotating station 1 to the cleaning liquid position P3 when the sample liquid L0 and the spot 103 are reacted. The position control means C4 moves the rotation station 1 to the antibody reagent position P4 when the cleaning of the sample liquid L0 is completed. Further, the position control means C4 moves the rotating station 1 to the cleaning liquid position P3 when the antibody reagent L2 and the spot 103 are reacted. The position control means C4 moves the rotation station 1 to the luminescent reagent position P5 when the cleaning of the antibody reagent L2 is completed. Further, the position control means C4 moves the rotating station 1 to the observation position P2 when the luminescent reagent L3 and the spot 103 are reacted. Further, the position control means C4 moves the rotary station 1 to the zero point position P1 when the observation is finished and the draining process is finished.

C5: Nozzle Lifting Unit A nozzle lifting unit C5 as an example of a supply unit moving unit lifts and lowers the nozzles 22 to 24 via the nozzle lifting circuit D2. The nozzle raising / lowering means C5 of Example 1 lowers the nozzles 22 to 24 to the injection position when the rotating station 1 moves to the cleaning liquid position P3, the antibody reagent position P4, and the luminescent reagent position P5. The nozzle lifting / lowering means C5 according to the first embodiment raises the nozzles 22 to 24 to the retracted position when the supply of the liquid from the nozzles 22 to 24 is completed.

C6: Cleaning Liquid Supply Unit The cleaning liquid supply unit C6 as an example of the cleaning liquid supply control unit drives the pump 32 to supply the cleaning liquid L1 from the cleaning liquid nozzle 22 to the reaction area A1 of the chip cassette S2. The cleaning liquid supply means C6 supplies the cleaning liquid L1 when the time T0 has elapsed since the sample liquid L0 was supplied to the reaction area A1. In addition, the cleaning liquid L1 is supplied when the time T0 ′ has elapsed since the antibody reagent L2 was supplied to the reaction area A1. Specifically, the cleaning liquid supply means C6 according to the first embodiment supplies the cleaning liquid L1 from the cleaning liquid nozzle 22 to the cassette chip S2 when the rotation station 1 moves to the cleaning liquid position P3 and the cleaning liquid nozzle 22 moves to the injection position. Inject.

C7: Antibody Reagent Supply Unit The antibody reagent supply unit C7 as an example of the antibody reagent supply control unit drives the pump 32 ′ to the antibody reagent from the nozzle 23 of the antibody reagent container to the reaction area A1 of the chip cassette S2. L2 is supplied. The antibody reagent supply means C7 supplies the antibody reagent L2 to the reaction area A2 when the sample liquid L0 is drained together with the cleaning liquid L1. Specifically, the antibody reagent supply means C7 of Example 1 is configured such that when the rotation station 1 moves to the antibody reagent position P4 and the nozzle 23 of the antibody reagent container moves to the injection position, the nozzle 23 of the antibody reagent container. The antibody reagent L2 is injected into the chip cassette S2.

C8: Luminescent Reagent Supply Unit As an example of the luminescent reagent supply control unit, the luminescent reagent supply unit C8 drives the pump 32 ″ to the luminescent reagent from the nozzle 24 of the luminescent reagent container to the reaction area A1 of the chip cassette S2. The luminescent reagent supply means C8 supplies the luminescent reagent L3 when the antibody reagent L2 in the reaction area A1 is drained together with the washing liquid L1. The supply means C8 injects the luminescent reagent L3 from the luminescent reagent container nozzle 24 into the chip cassette S2 when the rotation station 1 moves to the luminescent reagent position P5 and the luminescent reagent container nozzle 24 moves to the injection position. .

C9: Hood Lifting Unit The hood lifting unit C9 as an example of the dark box member control unit lifts and lowers the camera hood 47 via the hood lifting circuit D3. The hood elevating means C9 of the first embodiment lowers the camera hood 47 to the covering position when the rotating station 1 moves to the observation position P2. Further, the hood elevating means C9 of the first embodiment raises the camera hood 47 to the open position when the imaging of the camera 43 is completed.
C10: Image Storage Unit The image storage unit C10 as an example of the imaging control unit stores an image captured by the CCD 46 for a preset time T11.

C11: Image Analysis Unit Image analysis unit C11 as an example of an image processing unit performs an analysis process on a captured image. The image analysis unit C11 according to the first embodiment specifies the position of the spot 103 in the captured image data based on the position data of the designed spot 103 stored in advance. Then, the average intensity value of the spots is calculated based on the signal intensity of the image sensor that constitutes the identified spot 103. That is, the image analysis means C11 of Example 1 measures the average intensity value as being proportional to the specific IgE antibody concentration in the specimen corresponding to the antigen of the spot 103. In place of the average intensity value, the maximum signal intensity value or the intermediate value between the maximum signal intensity value and the adjacent peripheral value of the spot is calculated as a value proportional to the specific IgE antibody concentration in the sample. May be. Further, the image analysis unit C11 according to the first embodiment also performs a barcode reading process of the chip cassette S2 based on the image data captured by the camera 43. That is, the image analysis means C11 of Example 1 identifies the subject from the barcode of the imaged image data based on the correspondence information between the identifier and the subject information registered and stored in advance. Therefore, in Example 1, the subject is prevented from being mistaken for the measurement result.

C12: Display Unit The display unit C12 displays the measurement result processed by the image analysis unit C11 on the touch panel H2. The display unit C12 according to the first embodiment displays a captured image, an average intensity value for each spot 103 in the captured image data, and subject information. The maximum intensity value or intermediate value can also be displayed.
The configuration of the image analysis unit C11 and the display unit C12 is not limited to the configuration for displaying the brightness and the numerical value, and a conventionally known image analysis such as displaying the spot on the image data by color for each spot intensity. In addition, an image display configuration can be applied.
C13: Number-of-times discriminating means The number-of-times discriminating means C13 has a counter CT that counts the number of times J from when the cleaning liquid is supplied until the cleaning liquid is drained. The number determination means C13 determines whether or not the processing number J is larger than a preset threshold value J0.

C14: Time discriminating means The time discriminating means C14 has a timer TM for measuring time T0, T0 ', T1, T2, T3, T11. Then, the time discriminating means C14 discriminates whether or not the times T0 to T11 are up.
C15: Temperature control means The temperature control means C15 controls the micro heater 63 via the temperature control circuit D7 based on the temperature detected by the temperature sensor 64, and the lower surface of the rotation station 1 and the chip cassette S2 are set in advance. Hold at temperature.

(Description of Flowchart of Example 1)
Next, the processing flow of each program of the personal computer PC according to the first embodiment will be described using a flowchart.

(Explanation of flowchart of reaction observation process)
FIG. 6 is a flowchart of the reaction observation process according to the first embodiment of the present invention.
The processing of each ST (step) in the flowchart of FIG. 6 is performed according to a program stored in the HDD or the like of the computer main body H1. This process is executed in a multitasking manner in parallel with other various processes of the computer main body H1.

The flowchart shown in FIG. 6 is started when the reaction observation program AP1 is started in the personal computer PC.
In ST1 of FIG. 6, it is determined whether or not there is a start input from the input unit H2 of the personal computer PC. If yes (Y), the process proceeds to ST2. If no (N), ST1 is repeated.
In ST2, the reaction rotation process shown in FIG. 7 is executed. Then, the process proceeds to ST3.
In ST3, the cleaning process shown in FIG. 8 is executed. Then, the process proceeds to ST4.
In ST4, the antibody reagent process shown in FIG. 10 is executed. Then, the process proceeds to ST5.
In ST5, the cleaning process shown in FIG. 8 is executed. Then, the process proceeds to ST6.
In ST6, the luminescent reagent process shown in FIG. 12 is executed. Then, the process proceeds to ST7.
In ST7, the imaging process shown in FIG. 13 is executed. Then, the process proceeds to ST8.
In ST8, an end process shown in FIG. 14 is executed. Then, the process returns to ST1.

(Explanation of flowchart of reaction rotation process)
FIG. 7 is a flowchart of the reaction rotation process according to the first embodiment of the present invention, which is a subroutine of ST2 in FIG.
In ST101 of FIG. 7, the following processes (1) and (2) are executed. Then, the process proceeds to ST102.
(1) Start low-speed rotation.
(2) Set reaction time T0.
In ST102, it is determined whether or not the reaction time T0 is up. If yes (Y), the process proceeds to ST103, and if no (N), ST102 is repeated.
In ST103, the low speed rotation is terminated. Then, the reaction rotation process is terminated, and the process returns to ST (step) of the caller process.

(Description of flowchart of cleaning process)
FIG. 8 is a flowchart of the cleaning process according to the first embodiment of the present invention, and is a subroutine of ST3 and ST5 of FIG.
In ST201 of FIG. 8, it is assumed that J = 0. That is, the counter J is initialized. Then, the process proceeds to ST202.
In ST202, the rotation station 1 is moved to the cleaning liquid position P3. Then, the process proceeds to ST203.
In ST203, the nozzles 22 to 24 are moved to the injection position. Then, the process proceeds to ST204.
In ST204, the cleaning liquid L1 is injected into the chip cassette S2. Then, the process proceeds to ST205.
In ST205, the nozzles 22 to 24 are moved to the retracted position. Then, the process proceeds to ST206.
In ST206, the cleaning and draining process shown in FIG. 9 is executed. Then, the process proceeds to ST207.
In ST207, J = J + 1. That is, 1 is added to J. Then, the process proceeds to ST208.
In ST208, it is determined whether or not the counter J is equal to or greater than a threshold value J0. If yes (Y), the cleaning process is terminated, and the process returns to ST (step) of the calling process, and if no (N), the process returns to ST202.

(Description of flowchart of cleaning drainage process)
FIG. 9 is a flowchart of the cleaning drainage process according to the first embodiment of the present invention, which is a subroutine of ST206 in FIG.
In ST301 of FIG. 9, the following processes (1) and (2) are executed. Then, the process proceeds to ST302.
(1) Start low-speed rotation.
(2) The low speed time T1 is set.
In ST302, it is determined whether or not the low speed time T1 is up. If yes (Y), the process proceeds to ST303, and if no (N), ST302 is repeated.
In ST303, the low speed rotation is terminated. Then, the process proceeds to ST304.
In ST304, the following processes (1) and (2) are executed. Then, the process proceeds to ST305.
(1) Start medium speed rotation.
(2) The medium speed time T2 is set.
In ST305, it is determined whether or not the medium speed time T2 is up. If yes (Y), the process proceeds to ST306, and if no (N), ST305 is repeated.
In ST306, the medium speed rotation is terminated. Then, the process proceeds to ST307.

In ST307, the following processes (1) and (2) are executed. Then, the process proceeds to ST308.
(1) Start high-speed rotation.
(2) Set high-speed time T3.
In ST308, it is determined whether or not the high-speed time T3 is up. If yes (Y), the process proceeds to ST309, and if no (N), ST308 is repeated.
In ST309, the high speed rotation is terminated. Then, the cleaning and draining process is terminated, and the process returns to ST (step) of the calling process.

(Explanation of flowchart of antibody reagent processing)
FIG. 10 is a flowchart of the antibody reagent process of Example 1 of the present invention, which is a subroutine of ST4 in FIG.
In ST401 of FIG. 10, the rotation station 1 is moved to the antibody reagent position P4. Then, the process proceeds to ST402.
In ST402, the nozzles 22 to 24 are moved to the injection position. Then, the process proceeds to ST403.
In ST403, the antibody reagent L2 is injected. Then, the process proceeds to ST404.
In ST404, the nozzles 22 to 24 are moved to the retracted position. Then, the process proceeds to ST405.
In ST405, the antibody reagent reaction rotation process shown in FIG. 11 is executed. Then, the antibody reagent process is terminated, and the process returns to the ST (step) process of the caller process.

(Explanation of flowchart of antibody reagent reaction rotation process)
FIG. 11 is a flowchart of the reaction rotation process of the antibody reagent of Example 1 of the present invention, which is a subroutine of ST405 in FIG.
In ST101 ′ of the reaction rotation process of the antibody reagent in FIG. 11, the time T0 ′ for the reaction of the antibody reagent is used instead of the time T0 for the reaction of the sample solution. And different. Since the other processes are the same as those in FIG. 7, detailed description of the reaction rotation process of the antibody reagent is omitted.

(Description of flowchart of luminescent reagent processing)
FIG. 12 is a flowchart of the luminescent reagent process according to the first embodiment of the present invention, which is a subroutine of ST6 in FIG.
In ST501 of FIG. 12, the rotation station 1 is moved to the luminescent reagent position P5. Then, the process proceeds to ST502.
In ST502, the nozzles 22 to 24 are moved to the injection position. Then, the process proceeds to ST503.
In ST503, the luminescence reagent L3 is injected. Then, the process proceeds to ST504.
In ST504, the nozzles 22 to 24 are moved to the retracted position. Then, the luminescent reagent process is terminated, and the process returns to ST (step) of the caller process.

(Description of flowchart of imaging process)
FIG. 13 is a flowchart of the imaging process according to the first embodiment of the present invention, which is a subroutine of ST7 in FIG.
In ST601 of FIG. 13, the rotation station 1 is moved to the observation position P2. Then, the process proceeds to ST602.
In ST602, the camera hood 47 is moved to the covering position. Then, the process proceeds to ST603.

In ST603, the following processes (1) and (2) are executed. Then, the process proceeds to ST604.
(1) Start imaging.
(2) Set imaging time T11.
In ST604, it is determined whether or not the imaging time T11 is up. If yes (Y), the process proceeds to ST605, and if no (N), ST604 is repeated.
In ST605, imaging is terminated. Then, the process proceeds to ST606.
In ST606, the camera hood 47 is moved to the open position. Then, the imaging process ends, and the process returns to ST (step) of the calling process.

(Explanation of end processing flowchart)
FIG. 14 is a flowchart of end processing according to the first embodiment of the present invention, which is a subroutine of ST8 of FIG.
In ST701 of FIG. 14, the end drainage process shown in FIG. 15 is executed. Then, the process proceeds to ST702.
In ST702, the rotation station 1 is moved to the zero point position P1. Then, the termination process is terminated, and the process returns to ST (step) of the caller process.

(Explanation of flowchart of end drainage process)
FIG. 15 is a flowchart of the end drainage process according to the first embodiment of the present invention, which is a subroutine of ST701 in FIG.
15 is different from the cleaning and draining process of FIG. 9 in that ST301 to ST306 of the cleaning and draining process are omitted. Since other processes are the same as those in FIG. 9, detailed description of the end drainage process is omitted.

(Operation of Example 1)
In the diagnostic system S of the first embodiment having the above-described configuration, the chip cassette S2 is set at the zero point position P1 in the rotating station 1 of the diagnostic device S1. When the chip cassette S2 is set in the diagnostic apparatus S1, the chip cassette S2 of the first embodiment is an example of a test sample supply unit, and is injected using a pipette Pi shown in FIG. A test sample is injected from the hole 113a. In Example 1, as an example of a test sample, a sample liquid L0 based on blood collected from a subject is injected. Therefore, the sample liquid L0 is dropped onto the reaction area A1 of the chip cassette S2.
Further, in the set unit 2 of the rotation station 1, the temperature is held at a preset temperature by the temperature control mechanism 61. Therefore, in the reaction area A1, the sample liquid L0 and the spot 103 are easily reacted. When the processing start is input from the personal computer PC, the reaction monitoring process shown in FIG. 6 is executed in the diagnostic device S1.

FIG. 16 is an operation explanatory diagram of Embodiment 1 of the present invention, FIG. 16A is an explanatory diagram of a state in which a liquid is supplied to the reaction area, FIG. 16B is an explanatory diagram of a state in which a cleaning liquid is supplied to FIG. 16C is an explanatory diagram when rotating at a medium speed from FIG. 16B, and FIG. 16D is an explanatory diagram when rotating at a high speed from FIG. 16C.
In the diagnostic device S1, when the processing start is input, the rotating station 1 rotates at a low speed for a time T0. Therefore, the chip cassette S2 rotates at a low speed together with the rotation station 1. At this time, centrifugal force acts on the sample liquid L0 on the chip cassette S2. However, in the first embodiment, the first rotation speed N1 is set to a non-discharge rotation speed at which the sample liquid L0 becomes a centrifugal force that does not exceed the hydrophobic ring 102 due to surface tension or cohesive force. Yes. Therefore, as shown in FIG. 16A, the sample liquid L0 flows and stirs in the reaction area A1 without exceeding the hydrophobic ring 102. At this time, when a component to be detected, that is, an antibody specific to the antigen of the spot 103 is present in the sample liquid L0, it reacts with the antigen of the spot 103 to generate a so-called antigen-antibody reaction. The antigen is fixed as the spot 103, and can react with the antigen with a small amount of the sample liquid L0 as compared with the conventional configuration in which the antigen is not fixed at the spot 103.

In Example 1, the reaction time T0 is set to a time sufficient for the antigen-antibody reaction to occur. In addition, a large amount of antigen is added and fixed to each spot 103, and the decrease in the unreacted antigen due to the progress of the antigen-antibody reaction with the antibody in the sample liquid L0 may be ignored. As a result, the amount of specific IgE bound to the spot 103 is almost proportional to the concentration in the specimen. Therefore, it can be said that unreacted with the antigen of the spot 103 is suppressed despite the presence of a specific antibody in the sample liquid L0. When the time T0 has elapsed, the rotary station 1 moves to the cleaning liquid position P3.
When the rotation station 1 moves to the cleaning liquid position P3, the nozzle 22 moves to the injection position. That is, as shown in FIG. 16B, the lower end 22a of the cleaning liquid nozzle 22 enters the chip cassette S2 from the injection hole 113a. Then, the cleaning liquid L1 is supplied from the cleaning liquid nozzle 22 toward the reaction area A1. When a predetermined amount of the cleaning liquid L1 is supplied, the cleaning liquid nozzle 22 moves to the retracted position. In the first embodiment, in addition to the cleaning liquid nozzle 22, the nozzles 23 and 24 are also moved up and down integrally. Therefore, the number of lifting mechanisms is smaller than when the nozzles 22 to 24 are raised and lowered individually, and the configuration of the diagnostic device S1 is simplified and miniaturized. In addition, the number of lifting mechanisms is small and the cost is easily reduced.

When the cleaning liquid L1 is injected, a cleaning drainage process is executed. In the cleaning drainage process, the rotating station 1 rotates at a low speed during the low time T1. Therefore, as shown in FIG. 16B, the sample liquid L0 and the cleaning liquid L1 flow in the reaction area A1. Therefore, the sample liquid L0 and the cleaning liquid L1 are stirred and diluted, and the sample liquid L0 and the cleaning liquid L1 become familiar. The time T1 is set to a time when the liquid to be cleaned is sufficiently agitated and diluted with the cleaning liquid L1.
When the time T1 has elapsed, the rotation station 1 is rotated at a medium speed at the second rotation speed N2. Here, the second rotation speed N2 is set to a discharge rotation speed, and the liquid L0, L1 has a centrifugal force enough to move from the reaction area A1 over the hydrophobic ring 102 to the drainage area A2. Is set to Therefore, when rotated at medium speed, the mixed liquid of the sample liquid L0 and the cleaning liquid L1 gently exceeds the hydrophobic ring 102 as shown in FIG. 16C. Therefore, the liquids L0 and L1 are discharged from the reaction area A1 and moved to the drainage area A2 between the hydrophobic ring 102 and the cassette retaining wall 104.

  When the medium speed time T2 set to a time sufficient for the liquid to move from the reaction area A1 elapses, the rotation station 1 is rotated at a high speed at the third rotation speed N3. The third rotational speed N3 is set to a discharging rotational speed that is greater than the second rotational speed N2. Therefore, the centrifugal force also increases, and the liquid remaining in the drainage area A2 and the reaction area A1 moves toward the cassette retaining wall 104 by the action of the centrifugal force. Then, the liquids L <b> 0 and L <b> 1 are absorbed by the water absorbent 112 in the holding space 109 through the drain groove 111 of the cassette retaining wall 104. Thereby, the liquid is removed from the reaction area A1 and the drainage area A2, and the drainage of the chip cassette S2 is completed. The high speed rotation is continued until the high speed time T3 has elapsed. The high speed time T3 is set so that the liquid moved from the drainage area A2 or the like is sufficiently absorbed by the water absorbent 112. Therefore, it is difficult for the liquid to remain in the drainage area A2. In Example 1, the process until the cleaning liquid L1 is supplied and discharged is repeated a plurality of times.

  Here, as in the configurations described in Patent Documents 3 and 4, in the conventional configuration in which the liquid is sucked and discharged by the nozzle, the suction force can hardly reach only near the nozzle. Further, the surface tension or viscosity of the liquid acts on the liquid. Therefore, when the liquid is sucked and moved, the liquid runs out and is separated in the middle, and there is a possibility that a part of the liquid remains. Therefore, in order to reduce the remaining liquid, it is necessary to repeat the process of changing the position of the nozzle and sucking the remaining liquid. Therefore, in the conventional automated apparatus, it is necessary to provide a mechanism for moving the nozzle in order to specify the position where the liquid remains, or to adjust the position of the remaining liquid. This process is also time-consuming. Moreover, even with such a configuration, it is difficult to completely remove the liquid with the nozzle. In general, in the cleaning process, the supply of the cleaning liquid only dilutes the liquid to be removed, and the cleaning tends to be insufficient. Therefore, it is likely that it is necessary to repeat the process of supplying and draining the cleaning liquid a plurality of times. Therefore, in the conventional configuration, there is a problem that drainage takes time and labor, and the entire process becomes longer.

  On the other hand, in Example 1, it is the structure which drains using the centrifugal force which arises by rotation of the rotation station 1. FIG. That is, the liquid is absorbed by the water absorbing agent 112 in the cassette retaining wall 104 from the reaction area A1 or the drainage area A2 toward the cassette retaining wall 104 using centrifugal force. Here, in Example 1, the centrifugal force acts regardless of the position and distribution of the liquid. Therefore, unlike the conventional configuration, all the liquids in the reaction area A1 and the drainage area A2 can be moved by the rotation of the rotation station 1. Therefore, it is not necessary to move the liquid by repeating the suction operation. Therefore, in the first embodiment, the drainage process is easier than in the conventional configuration in which suction is performed by the nozzle. Therefore, in Example 1, the process of drainage is easy to finish in a short time.

  In addition, in the first embodiment, the liquid remaining in the areas A1 and A2 is easily reduced by adjusting the centrifugal force. That is, in the first embodiment, the plurality of rotation speeds N1 to N3 are used to discharge the cleaning liquid L1 and the like by applying centrifugal forces of different magnitudes. That is, first, the sample liquid L0 and the cleaning liquid L1 are made to acclimate in the reaction area A1 by performing a low-speed rotation, so that the sample liquid L0 can be easily drained. Thereafter, the liquids L0 and L1 are gently discharged from the reaction area A1 to the drainage area A2 at medium speed rotation. Here, when the medium speed rotation is omitted and the liquid is suddenly discharged at a high speed, a large centrifugal force acts on the liquids L0 and L1 in the reaction area A1. Therefore, the droplets are likely to be generated, and there is a possibility that the droplets adhere to the seal 113 portion above the reaction area A1. Further, the liquid running out phenomenon is likely to occur, and there is a possibility that the liquid remains in the reaction area A1. On the other hand, in Example 1, the liquid is gently moved to the drainage area A2 at medium speed rotation, and then is rotated at high speed. Therefore, a large centrifugal force is acting in a state where there is little liquid remaining in the reaction area A1, and it is possible to suppress the possibility that splashes adhere to the seal 113 portion of the reaction area A1 and the liquid remains in the reaction area A1. Has been. Therefore, in Example 1, the achievement degree of drainage and washing | cleaning is high. Therefore, in Example 1, it is easy to reduce the number of times J0 to repeat the processing until the cleaning liquid L1 is supplied and drained, and the processing time spent for the entire inspection is shortened. Further, since the number of times J0 is repeated is reduced, the amount of the supplied cleaning liquid L1 can be reduced, and the total amount of liquid to be drained can be easily reduced.

Further, in the first embodiment, the position of the set portion 2 is formed at a position separated from the rotary shaft 3 in the radial direction. Therefore, the liquids L0 and L1 in the chip cassette S2 are likely to be far from the center of rotation, and the centrifugal force is likely to increase even if the rotational speed of the rotary shaft 3 is the same. Therefore, in Example 1, it is easy to drain the liquid at a smaller rotational speed than in the case where the set unit 2 exists on the center of rotation.
Moreover, in the conventional structure, the tube and tank for drainage are needed. On the other hand, in Example 1, it is the structure which makes the water absorbing agent 112 in chip | tip cassette S2 absorb and hold a liquid. Accordingly, in the first embodiment, the drainage tube and tank are omitted. Therefore, compared with the conventional configuration, the diagnostic apparatus S1 is simplified and downsized. Further, there is no need for a drainage tank and the cost is easily reduced. In the first embodiment in which the drainage tank is omitted, the work of discarding the liquid from the drainage tank is unnecessary, and the workability and operability of the diagnosis system S are easily improved.

  In Patent Document 4, it is described that the chip cassette is tilted or the liquid is blown and sprayed when the drainage process is performed. However, in these configurations, in addition to the configuration for moving the chip cassette, a configuration for tilting and a configuration for blowing are required. Therefore, the apparatus becomes complicated and the entire apparatus tends to be large. On the other hand, in the first embodiment, the liquid in the chip cassette S2 is also moved by using the rotation of the rotation station 1 for moving the chip cassette S2. That is, in Example 1, the mechanism for moving the chip cassette S2 and the mechanism for moving the liquid in the chip cassette S2 are shared. Therefore, in Example 1, the whole structure is simplified and reduced in size.

  In the first embodiment, the chip cassette S2 having the water absorbing agent 112, the seal 113, and the like is used. Here, as in Patent Documents 3 and 4, a chip cassette in which the spot 103 is exposed to the outside, that is, a so-called open chip configuration is also conceivable. However, in the open chip, there is a possibility that the sample liquid L0, the cleaning liquid L1, and the like may be scattered outside when centrifugal force is applied. Therefore, there is a possibility that the diagnostic apparatus S1, the inspection environment, and the worker are contaminated. In addition, foreign matter may enter the chip, or the operator may touch the reaction areas A1 and A2 when the chip is mounted on the rotating station 1. In addition, liquids such as the sample liquid L0 may evaporate during processing. Therefore, in the open chip, the spot 103 may be damaged or the sample liquid may be insufficient, which may adversely affect the inspection accuracy. Therefore, with an open chip, careful work is easily required, and workability and operability are likely to deteriorate.

  On the other hand, the chip cassette S2 of the first embodiment includes a water absorbing agent 112 and a seal 113. Therefore, the areas A1 and A2 are covered with the cassette retaining wall 104 and the seal 113, and even when centrifugal force is applied, the specimen liquid L0, the cleaning liquid L1, and the like are prevented from being scattered outside. Further, evaporation of the sample liquid L0 and the like is suppressed. In addition, the liquids L0 and L1 moved to the drainage area A2 are absorbed by the water absorbent 112 and held in the chip cassette S2. That is, the chip cassette S2 of the first embodiment has a closed configuration in which the liquid is difficult to flow out to the outside. Therefore, the chip cassette S2 of the first embodiment is easier to handle than the open chip, and the operability of the diagnostic system S is improved. In particular, in Example 1 in which the number of times J0 is repeated and the amount of drainage tends to be small, the drainage is not easily absorbed and the leakage is easily suppressed, and the water absorbing agent that absorbs the drainage and the space for storing the drainage are stored. The chip cassette S2 having a closed configuration can be preferably used while maintaining a compact configuration.

  When the cleaning of the sample liquid L0 is completed, the rotation station 1 moves to the antibody reagent position P4. In FIG. 16, at the antibody reagent position P4, the nozzle 23 of the antibody reagent container moves to the injection position, and the antibody reagent L2 is supplied and injected into the chip cassette S2. Therefore, in the reaction area A1, the labeled antibody reagent L2 reacts with the IgE antibody bound to the allergen of each spot 103 with the antigen antibody, and a labeling reaction occurs. When the nozzle 23 of the antibody reagent container moves to the retracted position, the rotation station 1 rotates at a low speed for a time T0 ′. Therefore, the antibody reagent L2 is stirred in the reaction area A1. Therefore, the reaction efficiency is improved. The reaction time T0 ′ is set to a time sufficient for the labeling reaction to occur. When the low-speed rotation at time T0 ′ is completed, the washing process is executed, and the antibody reagent L2 is washed in the same manner as the sample liquid L0.

  When the antibody reagent L2 is washed, the rotation station 1 moves to the luminescent reagent position P5. At the luminescent reagent position P5, the nozzle 24 of the luminescent reagent container moves to the injection position, and the luminescent reagent L3 is supplied and injected into the chip cassette S2. Therefore, in the reaction area A1, the luminescent reagent L3 reacts with the spot 103 where the labeling reaction has occurred, and a chemiluminescent reaction occurs. That is, the spot 103 emits light according to the amount of the antibody that has reacted with the antigen. When the nozzle 24 of the luminescent reagent container moves to the retracted position, the rotation station 1 moves to the observation position P2. When the rotation station 1 moves to the observation position P2, the camera hood 47 moves to the covering position and shields the chip cassette S2 from the outside. Therefore, the chip cassette S2 is closed with a dark box, and the emitted light from the spot 103 is imaged by the CCD 46 for a time T11.

  Here, in Example 1 in which the cleaning process is performed using centrifugal force, the achievement degree of the cleaning is high, and the background noise in the captured image is easily reduced. Therefore, in the first embodiment, the inspection accuracy is likely to be higher than the conventional configuration. In Example 1, high-speed rotation is performed after the liquid is gently discharged to the drainage area A2 by medium-speed rotation. Therefore, it is suppressed that a splash splashes above reaction area A1, and soils seal 113. Therefore, it is also suppressed that the splash generated by the centrifugal force adversely affects the observation of the spot 103. In particular, in FIG. 4A, the injection hole 113 a of the seal of Example 1 does not overlap with the spot 103. Therefore, when the camera 43 captures an image from above, the emitted light from the spot 103 is not scattered by the injection hole 113a. Therefore, the position of the spot 103 is difficult to shift on the captured image, and the possibility that the position of the emitted spot 103 is misidentified is reduced. In addition, the board | substrate 101 and the seal | sticker 113 of Example 1 are produced with the material which has the optically excellent characteristic. Therefore, it is easy to ensure high reliability of chemiluminescence measurement.

The image captured by the camera 43 is analyzed. In the first embodiment, image data corresponding to the light emission intensity of the spot 103 and numerical data are displayed on the display H2. Therefore, it is possible to determine the amount of antibody in the sample liquid L0.
When the imaging by the camera 43 is completed, the camera hood 47 moves to the open position. And the process which drains the luminescent reagent L3 is performed. That is, the rotation station 1 rotates at high speed for a high time T3. Thereby, the luminescent reagent L3 moves by centrifugal force and is absorbed by the water-absorbing agent 112. In addition, when draining the luminescent reagent L3, only high-speed rotation is performed without performing low-speed rotation or medium-speed rotation. Therefore, the processing time for drainage is shortened. When drainage of the luminescent reagent L3 is completed, the rotation station 1 moves to the zero point position P1 and is held.

  Therefore, the chip cassette S2 can be taken out from the diagnostic device S1, and the chip cassette S2 can be replaced. The liquids L0 to L3 injected into the chip cassette S2 are absorbed by the water absorbing agent 112 and can be discarded for each chip cassette S2. Further, the liquids L0 to L3 are absorbed by the water-absorbing agent 112, and the liquids L0 to L3 are unlikely to jump out of the water injection hole 113a when the chip cassette S2 is taken out from the diagnostic device S1 and carried. Therefore, in Example 1, the possibility that the liquids L0 to L3 flow out of the chip cassette S2 is reduced. Therefore, in Example 1 using the chip cassette S2 having a closed configuration, the operator is less likely to touch the liquids L0 to L3, the spot 103, and the like as compared with the open chip, and safety is improved. In addition, the chip cassette S2 is easy to handle, and the operability is improved.

(Experimental example)
Next, an experiment for confirming the effect of Example 1 was performed.
(Experimental example 1)
In Experimental Example 1, an experiment was performed to confirm whether or not the liquid in the chip cassette S2 can be removed by centrifugal force, that is, whether or not the liquid can be drained. In Experimental Example 1, the chip cassette was rotated at the rotation station 1 and the amount of remaining liquid remaining in the rotated chip cassette was measured. Here, in Experimental Example 1, the spot 103, the cassette retaining wall 104, the water absorbing agent 112, and the seal 113 were omitted from the chip cassette S2, and a so-called bare substrate including only the substrate 101 and the hydrophobic ring 102 was used. . That is, the substrate of Experimental Example 1 is configured such that the liquid can be scattered from the substrate when a centrifugal force is applied. Then, based on the amount of change of the liquid before and after being rotated at the rotation station 1, the amount of the remaining liquid on the substrate was measured.

  Specifically, in Experimental Example 1, first, the weight α1 of the bare substrate is measured. Next, a preset amount α0 of the cleaning liquid is dropped into the reaction area A1. Then, after the dropped bare substrate is rotated at the rotation station 1, the weight α2 of the bare substrate after the rotation is measured. Therefore, the remaining liquid amount remaining on the substrate is measured as α2−α1. In Experimental Example 1, three types of cleaning solutions were used as cleaning solutions: TBS: Tris-Buffered Saline, TBST: Tris-buffered saline-Tween 20, and a dedicated cleaning solution prepared for the diagnostic system S. The inner diameter of the hydrophobic ring 102 was set to φ18 [mm]. The weight was measured using an electronic balance, and the decrease in liquid volume due to evaporation during measurement was ignored.

FIG. 17 is an explanatory diagram of the experimental results of Experimental Example 1.
FIG. 17 shows the relationship between the number of rotations and the amount of remaining liquid when the rotation station 1 is rotated at the number of rotations. In FIG. 17, the horizontal axis represents the number of revolutions [rpm], and the vertical axis represents the remaining liquid amount [μL]. In FIG. 17, when the rotational speed is close to 0, the residual liquid amount is the same value in any of TBS, TBST, and the dedicated cleaning liquid. Further, the value does not change unless the rotational speed is increased to a certain degree. Therefore, when the rotation speed is close to 0, it was confirmed that the cleaning liquid of the amount α0 supplied to the reaction area A1 is held in the reaction area A1.

On the other hand, it was confirmed that when the number of revolutions was large to some extent, the amount of residual liquid remaining on the substrate decreased as the number of revolutions was increased. At this time, TBS and TBST may remain more easily than the dedicated cleaning liquid, but the remaining liquid amount decreased in any cleaning liquid as the number of rotations increased. In particular, it has been confirmed that at any rotational speed sufficiently higher than 1000, any cleaning liquid only has a residual liquid amount of about 1/1000 compared to a rotational speed close to zero.
Therefore, it was confirmed that the liquid can be removed from the chip cassette S2 by the centrifugal force, and the diagnostic system S using the centrifugal force can drain the liquid. It was also confirmed that the diagnostic system S using centrifugal force can be drained regardless of the type of cleaning liquid. In the diagnostic system S using centrifugal force, it was also confirmed that the cleaning liquid can be held in the reaction area A1 or drained from the substrate by properly using the rotation speed.

(Experimental example 2)
In Experimental Example 2, an experiment was conducted to examine the relationship between the number of cleaning steps and the degree of cleaning achievement. In Experimental Example 2, the reaction observation process was executed using the diagnostic system S of Example 1, and the emission intensity of the spot 103, that is, the signal intensity of the CCD 46 that received the light from the spot 103 was observed. In Experimental Example 2, instead of the chip cassette S2 of Example 1, a chip cassette in which the spot 103 was omitted was used. The inner diameter of the hydrophobic ring 102 was set to φ18 [mm]. In Experimental Example 2, a labeled antibody reagent was added and rotated at a low speed for stirring with a time T0 ′ of 4 minutes. After that, a cleaning process was performed in which the cleaning liquid was supplied and the cleaning liquid was drained. The number J0 of repeating the washing process was set to 2 times and 10 times. Then, for each of the cases where the washing process was repeated twice and ten times, an integrated image of 60 seconds after the reaction of the luminescent reagent was taken, and the average signal intensity of the entire reaction area was obtained as the background signal intensity. When the antibody reagent is supplied to the chip cassette, the remaining amount of the antibody reagent becomes smaller as the degree of cleaning is higher. Therefore, the chemiluminescence reaction between the antibody reagent and the luminescent reagent is reduced, and the observed background signal intensity is weakened. On the contrary, if the achievement degree of washing is low, the remaining amount of the antibody reagent is increased and the chemiluminescence reaction with the luminescent reagent is increased, so that the intensity of the observed background light is increased. Therefore, the degree of cleaning achievement can be confirmed by the strength of the observed background signal intensity.

(Comparative Example 1)
In Comparative Example 1, the signal intensity was observed using the biochip automatic analysis system described in Patent Document 3 instead of the diagnostic system S of Example 1. That is, the comparative example 1 is different from the experimental example 2 in that the liquid is sucked by the nozzle and discharged. In Comparative Example 1, conditions and measurement methods other than those necessary for the nozzle system of Comparative Example 1 were the same as in Experimental Example 2.

FIG. 18 is an explanatory diagram of experimental results of Experimental Example 2 and Comparative Example 1.
In FIG. 18, in Comparative Example 1, the background signal intensity was about 5000 when the number of times the cleaning process was repeated was 2. And when the frequency | count of repeating a washing | cleaning process was increased to 10 times, the background light signal intensity | strength reduced to about 1000. Therefore, it was confirmed that in the comparative example 1 using the nozzle, it is necessary to repeat the cleaning process 10 times or more.
On the other hand, in Experimental Example 2 using the diagnostic system S of Example 1, the background signal intensity was 500 or less regardless of whether the cleaning process was repeated twice or ten times. In particular, in Experimental Example 2, when the number of times the cleaning process was repeated was 10, the background signal intensity was 1/10 or less compared to the case of 2 times. Therefore, it was confirmed that the diagnostic system S of Example 1 using the centrifugal force has higher cleaning achievement than the nozzle configuration. Therefore, in the diagnostic system S of the first embodiment, the reagent hardly remains and the background signal intensity is reduced. That is, it was confirmed that the inspection accuracy was increased. In addition, since the number of times of cleaning is smaller than that of the nozzle configuration, it is confirmed that the inspection time can be shortened and the cleaning liquid is easily reduced.

(Experimental example 3)
19 is an explanatory diagram of the experiment of Experimental Example 3, FIG. 19A is an explanatory diagram of spot allergens, FIG. 19B is an explanatory diagram of observation results of the first specimen liquid, and FIG. 19C is an observation result of the second specimen liquid. FIG. 19D is an explanatory diagram of the observation result of the third specimen liquid.
In Experimental Example 3, an experiment for detecting an anti-allergen antibody was performed. In Experimental Example 3, the experiment was performed by observing with the diagnostic device S1 using the chip cassette S2 in which the allergen is arranged as the spot 103. In FIG. 19A, in Experimental Example 1, a total of 24 spots 103 were arranged, 4 vertically and 6 horizontally. The six spots 103a in the first row have a leopard mite, the cats have six spots 103b in the second row, the milk has six spots 103c in the third row, the six spots 103d in the fourth row have Each antigen of the lampaku was fixed. Then, sample liquids derived from the three allergic patients A, B, and C were observed using the chip cassette S2.

  The observation results are shown in FIGS. 19B to 19D. As shown in FIGS. 19B to 19D, it was confirmed that when the patients were different, the signal intensity was different depending on the allergen species. That is, it was confirmed that although the concentration of specific IgE antibody differs depending on the patient, the signal intensity differs accordingly. Therefore, it was confirmed that the diagnostic system S of Example 1 can determine the concentration of the specific IgE antibody in the specimen against the allergen.

(Experimental example 4)
FIG. 20 is an explanatory diagram of the observation result of Experimental Example 4, FIG. 20A is a diagram showing the relationship between the signal intensity of the standard sample solution and the CAP value, FIG. FIG. 20C is a diagram showing the relationship between signal intensity and CAP value when measuring mite allergen.
In Experimental Example 4, the correlation between the signal intensity and the CAP value, that is, the correlation between the signal intensity measured using the diagnostic system S of the present application and the concentration measured using the CAP method is examined. Went.

  FIG. 20A and FIG. 20B show signal intensities when the standard sample solution is used. Here, the standard sample solution is a sample solution prepared according to the determination classification based on the correlation with the CAP value. Specifically, class 0 (0 to 0.35: negative), class 1 (0.35 to 0.7: false positive), class 2 (0.7 to 3.5: weakly positive), class 3 (3 .5 to 17.5: positive, CAP value indicating boundary values of class 4 (17.5 to 50: positive), class 5 (50 to 100: strong positive), class 6 (100 or more: strong positive) 7 specimen liquids with IgE concentrations prepared in advance so that The standard sample solution was used to create a standard curve for signal intensity calibration.

  FIG. 20C shows the result of measuring mite allergen using a plurality of different specimen fluids collected from a person. That is, FIG. 20C shows the relationship between the signal intensity when the mite allergen is immobilized as the spot 103 in the same chip cassette S2 as in Experimental Example 1, and the concentration of the mite-specific IgE antibody separately measured by the CAP method. . In FIG. 20C, the vertical axis represents the signal intensity, and the horizontal axis represents the CAP value. Therefore, FIG. 20C confirmed that the signal intensity observed by the diagnostic system S has a high correlation with the value measured by the CAP method.

(Experimental example 5)
In Experimental Example 5, an experiment for measuring the coincidence rate of class determination was performed. The determination classification matching rate based on the correlation between the four types of allergen data obtained by the diagnostic system S and the CAP value shown in FIG. 20 was measured. In Experimental Example 5, the class coincidence rate was measured for seven stages of class 0 to class 6.
Table 1 shows the measurement results. High class match rates were obtained for ticks, cats, milk, and lampaku. Therefore, it was confirmed that the reliability of the multi-item simultaneous analysis of the diagnostic system S using the chip cassette S2 according to Example 1 is high.

(Experimental example 6)
FIG. 21 is an explanatory diagram of Experimental Example 6, FIG. 21A is an explanatory diagram of spot arrangement positions, and FIG. 21B is an explanatory diagram of observation results of a chip cassette.
In Experimental Example 6, an experiment for detecting a virus antigen antibody was performed. In FIG. 21A, in Experimental Example 6, a measles, rubella, chickenpox, mumps, EB (Epstein-Barn virus) detoxified virus (antigen), and anti-IgG antibody as a positive control (positive control in the figure), As negative control (negative control in the figure), two BSA (bovine serum albumin) were arranged as spots a to g, respectively. That is, spots a to g were arranged in the order of chickenpox, EB, mumps, rubella, negative control, positive control, and measles. The fixed amount of virus or the like is in the range of 0.5 [mg / mL] to 1.5 [mg / mL].
A serum collected from a human body and diluted was prepared, and a detection reaction was performed under the same conditions as in Experimental Example 3 except that the detection antibody was replaced with IgG.

  FIG. 21B shows the observation result. It can be seen that the signal intensity varies depending on the spots a to g, and the antibody titer differs for each virus. This antibody titer was confirmed to be consistent with the standard assay EIA (Enzyme Immunoassay). Therefore, it was confirmed that the diagnostic system S of Example 1 of the present invention is applicable to tests other than allergy diagnosis. In particular, in the diagnostic system S of the first embodiment, the chip cassette S2 has a closed configuration, and operability and safety are improved. Therefore, it was confirmed that it can be suitably applied to virus inspection.

(Summary)
Based on Experimental Examples 1 to 6, the differences in configurations corresponding to Examples, Patent Documents 1 to 4 and Non-Patent Document 5 are shown in Tables 2 and 3 below.

  In Table 2, the number of simultaneous inspection items is larger in Experimental Examples 3 to 6 than in the MAST method or the microarray method. In Experimental Examples 3 to 6, the time from when the chip cassette S2 is mounted on the rotary station 1 and the start is input until the chip cassette S2 returns to the zero point position is about 15 minutes. In contrast, the MAST method takes 6 hours and the microarray method takes 30 minutes or more. Therefore, in Experimental Examples 3 to 6, the measurement time is shorter than that of the conventional MAST method or microarray method. Furthermore, the amount of the sample liquid is also smaller than that of the MAST method or the microarray method. Therefore, it is understood that the present embodiment is more useful than the MAST method and the microarray method.

  In Table 3, when the level was the same as that of Comparative Example 4 with Comparative Example 4 as a reference, x was given. Moreover, when it has the advantage compared with the comparative example 4, (circle) was attached | subjected. Furthermore, when it has the advantage compared with the structure marked with ◎, ◎ is marked. The configuration of the example is superior to the comparative example 4 in the number of inspection items, but is at the same level as the configurations of the comparative examples 5 and 6. However, as can be understood from Experimental Examples 1 and 2, in the present embodiment using centrifugal force, the inspection accuracy is improved and the inspection time is shortened as compared with the configurations of Comparative Examples 5 and 6 in which the liquid is discharged by the nozzle. The Further, in the embodiment of the present application, the chip cassette has a closed configuration, and operability and safety are improved as compared with Comparative Examples 5 and 6 of the open chip. In the configurations of Comparative Examples 5 and 6, since a nozzle is used, a drainage tank or the like is required. However, in the present embodiment, the drainage tank is unnecessary and it is easy to reduce the size. In addition, the installation area of diagnostic apparatus S1 of Experimental Examples 3-6 is realizable by about A4 size. Therefore, in various respects, it can be understood that the configuration of the present embodiment is more useful than the immunochromatography method and the configuration of the nozzle and the open chip.

Next, a second embodiment of the present invention will be described. In the description of the second embodiment, components corresponding to the components of the first embodiment are denoted by the same reference numerals, and detailed description thereof is omitted. To do.
This embodiment is different from the first embodiment in the following points, but is configured in the same manner as the first embodiment in other points.

(Description of chip cassette S2 'of Example 2)
22 is an explanatory view of a chip cassette according to the second embodiment of the present invention, FIG. 22A is a plan view corresponding to FIG. 4A of the first embodiment, and FIG. 22B is a sectional view taken along the line XXIIB-XXIIB in FIG. It is a figure corresponding to FIG. 4B of Example 1. FIG.
In FIG. 22, a chip cassette S2 ′ as an example of the inspection substrate of the second embodiment is replaced with a hydrophobic ring 102 ′ and a seal 113 ′ instead of the hydrophobic ring 102 and the seal 113 of the chip cassette S2 of the first embodiment. And have.

The hydrophobic inclined portion 102 ′, which is an example of the separation portion of the second embodiment and is an example of the hydrophobic portion, is formed in an annular shape. The hydrophobic inclined portion 102 'has an inclined surface 102a' inclined upward as it goes radially outward. The inclined surface 102a 'is hydrophobized. On the outer side in the radial direction of the inclined surface 102a ', a water shielding portion 102b' as an example of a standing wall is formed.
Further, the seal 113 ′ as an example of the covering member of the second embodiment is disposed at a position where the injection hole 113 a ′ overlaps with the hydrophobic inclined portion 102 ′ in FIG. 22A as viewed from above. The nozzles 22 to 24 of the second embodiment are arranged according to the position of the injection hole 113a ′.
In the chip cassette S2 ′ of the second embodiment, nine spots 103 are arranged.

The chip cassette S2 'according to the second embodiment is formed symmetrically in the front-rear and left-right directions except for the position of the injection hole 113a'. Here, in the chip cassette S2 ′ of the second embodiment, the length λ1 from the center position O to the inner end of the hydrophobic inclined portion 102 ′ in the left-right direction of FIG. 22B is, for example, 3.5 [mm]. Is set. The length λ2 from the center position O to the water shielding portion 102b ′ of the hydrophobic inclined portion 102 ′ is set to 7 [mm]. Further, the length λ3 from the central position O to the inner wall portion 108 of the cassette retaining wall 104 is set to 10 [mm]. The length λ4 from the center position O to the outer wall portion 108 of the cassette retaining wall 104 is set to 17 [mm]. In the vertical direction, the thickness λ5 of the substrate 101 is set to 1 [mm]. Further, the height λ6 of the outer wall portion 102b ′ of the hydrophobic inclined portion 102 ′ is set to 1.5 [mm]. Further, the length λ7 from the lower portion of the substrate 101 to the upper surface 107b of the cassette retaining wall is set to 6 [mm]. Regarding the lengths λ1 to λ7, the exemplified specific numerical values can be changed to arbitrary numerical values within the range where the operation and effect of the present invention are achieved.
In the inspection apparatus S1 according to the second embodiment, the setting unit 2 and the nozzles 22 to 24 are arranged according to the shape of the chip cassette S2 ′.

(Operation of Example 2)
In the diagnostic system S of the second embodiment, the chip cassette S2 ′ of the second embodiment is used instead of the chip cassette S2 of the first embodiment. Also in the chip cassette S2 ′ of the second embodiment, the sample liquid L0 is injected from the injection hole 113a ′. When the sample liquid L0 falls from the injection hole 113a ′, it moves on the hydrophobic inclined portion 102 ′ by the action of gravity. Therefore, the sample liquid L0 moves to the reaction area A1 and can react with the spot 103.
Here, in Example 2, when there is a start input from the personal computer PC, the same reaction observation process as in Example 1 is executed. Therefore, as in the first embodiment, the rotating station 1 rotates and the drainage process is performed. Therefore, in the second embodiment, as in the first embodiment, the inspection accuracy is improved and the inspection time is shortened. In addition, the chip cassette S2 ′ of the second embodiment also uses the chip cassette S2 ′ having a closed configuration including the water absorbing agent 112 and the seal 113 ′. Therefore, like the first embodiment, the operability is improved and the safety is enhanced.

  In particular, in the chip cassette S2 ′ of Example 2, the inclined surface 102a ′ is formed on the hydrophobic inclined portion 102 ′. Therefore, even if the centrifugal force acts to move the liquid from the reaction area A1 on the hydrophobic inclined portion 102 ', the liquid easily returns to the reaction area A1 by the action of gravity. Therefore, in the second embodiment, compared to the first embodiment, the liquid is less likely to overflow from the reaction area A1, and the first rotation speed N1 can be increased. When the drainage process is executed, the liquid in the reaction area A1 moves on the inclined surface 102a and moves to the drainage area A2. Then, when the liquid moves to the drainage area A2, the return to the reaction area A1 is blocked by the water blocking section 102b of the hydrophobic inclined section 102 ′. Therefore, compared with the case where it is not the structure obstruct | occluded with a wall-shaped member, in Example 2, it is prevented reliably that it returns from drainage area A2 to reaction area A1. In Example 2, the injection hole 113a ′ does not overlap the position of the spot 103 when viewed from above. Therefore, in the second embodiment, similarly to the first embodiment, adverse effects on imaging are suppressed.

Next, the third embodiment of the present invention will be described. In the description of the third embodiment, the same reference numerals are given to the components corresponding to the components of the first and second embodiments, and the detailed description thereof will be given. Is omitted.
This embodiment is different from the first embodiment in the following points, but is configured in the same manner as the first embodiment in other points.

(Description of diagnostic device S1 ')
(Description of rotating station 1 ')
FIG. 23 is an explanatory diagram of the main part of the diagnostic system of Example 3 of the present invention, FIG. 23A is an explanatory diagram of the rotating station, FIG. 23B is a case where the rotating station is moved to the zero point position and the rotating unit is moved to the reference position FIG. 23C is an explanatory view of a coil spring on the rotation station of FIG. 23B.
In FIG. 23, a shaft support portion 71 is formed in the rotation station 1 ′ of the diagnostic device S1 ′ of the third embodiment instead of the set portion 2 of the first embodiment. A rotating shaft 73 extending upward is supported by the shaft support portion 71 via a bearing 72 as an example of a bearing member. At the upper end of the rotating shaft 73, a rotating part 74, which is an example of a swinging table and is an example of a second rotating table, is fixedly supported. Therefore, the rotating portion 74 is supported so as to be rotatable integrally with the rotating shaft 73 with respect to the rotating station 1 ′.

  In FIG. 23, a set portion 2 ′ similar to the set portion 2 of the first embodiment is formed on the rotating portion 74. Therefore, in the third embodiment, the chip cassette S2 is detachably supported with respect to the set portion 2 ′ of the rotating portion 74 that is rotatably supported by the rotating station 1 ′. In Example 3, when the chip cassette S2 is mounted on the set part 2 ′, the reaction part A1 is arranged so that the center part thereof corresponds to the rotation center of the rotating part. That is, in the third embodiment, the set portion 2 ′ is configured so that the injection hole 113 a of the chip cassette S 2 matches the rotation center of the rotation portion 74.

  23A and 23C, a coil spring 76 as an example of an elastic member is fixed below the rotation shaft 73. The coil spring 76 is wound around the rotary shaft 73. That is, the coil spring 76 according to the third embodiment is fixed in a state where the main body portion 76a is attached to the spring fixing portion 73a. Further, one end 76b of the coil spring 76 is supported by a first spring support portion 77 provided in the rotation station 1 '. Further, the other end 76c is supported by a second spring support 78 provided in the rotation station 1 ′. Therefore, when the rotating portion 74 rotates relative to the rotating station 1 ′ together with the rotating shaft 73, the positional relationship between the coil spring 76 and the spring support portions 77 and 78 changes, and the coil spring 76 is elastically deformed. Here, in the third embodiment, the coil spring 76 is configured such that the rotating portion 74 has a natural length at the reference position P11 illustrated in FIG. 23B.

  Therefore, when the rotating portion 74 is relatively rotated from the reference position P11, the coil spring 76 is elastically deformed and the elastic force is increased regardless of the rotating direction of the rotating portion 74. Then, when the elastic force of the coil spring 76 is increased and the rotation of the rotating portion 74 is stopped, the coil spring 76 starts elastic recovery. Accordingly, the coil spring 76 is restored toward the natural-length reference position P11, and the rotation shaft 73 and the rotation unit 74 are relatively rotated toward the reference position P11. Therefore, in the third embodiment, the rotating unit 74 can rotate forward and backward with respect to the rotating station 1 ′, and can swing and rotate with reference to the reference position P <b> 11 by the action of the coil spring 76.

In the third embodiment, the rotation angle of the rotating unit 74 with respect to the rotating station 1 ′ is regulated by the coil spring 76. That is, the elastic constant of the coil spring 73 is set so that the rotation angle of the rotating unit 74 is within ± 90 degrees from the reference position P11. In the third embodiment, the elastic constant of the coil spring 76 is an elastic constant that enables the rotating unit 74 to move from the reference position P11 to a position with a rotation angle of ± 90 degrees when the rotation station 1 ′ rotates at a high speed N3. Is set.
The bearing 72, the rotation shaft 73, the coil spring 76, and the spring support portions 77 and 78 constitute a rotation mechanism 81 of the rotation section as an example of the second rotation mechanism of the third embodiment.

In FIG. 23A, a temperature control mechanism 61 ′ is supported on the rotation station 1 ′ of the third embodiment. That is, the micro heater 63 and the temperature sensor 64 are supported by the rotation station 1 ′ via the support member 62 ′ corresponding to the lower part of the rotation unit 74.
A slip ring 91 as an example of an electric transmission member is supported on the rotation shaft 3 ′ of the rotation station 1 ′ so as to correspond between the rotation shaft 3 ′ and the rotation station 1 ′. A micro heater 63 and a temperature sensor 64 are electrically connected to the computer PC via the slip ring 91.
Embodiment 3 includes the rotation station 1 ′, the rotation mechanism 4, the position detection mechanism 13, the nozzle device 21, the camera device 41, the temperature control mechanism 61 ′, the rotation unit 74, the rotation mechanism 81 of the rotation unit, the slip ring 91, and the like. The diagnostic device S1 'is configured.

(Operation of Example 3)
In the diagnostic system S of the third embodiment, the diagnostic device S1 ′ of the third embodiment is used instead of the diagnostic device S1 of the first embodiment. That is, in the third embodiment, the chip cassette S2 is set on the set portion 2 ′ of the rotating portion 74 supported on the rotating station 1 ′. Then, the sample liquid L0 is injected into the chip cassette S2, and the reaction observation process is executed as in the first embodiment. Therefore, also in the third embodiment, the inspection accuracy is improved and the inspection time is shortened, and the same effects as the first embodiment are obtained. In particular, in the third embodiment, the rotating portion 74 in which the set portion 2 'is formed is supported so as to be rotatable with respect to the rotating station 1'. That is, when the rotation station 1 'rotates, the rotation unit 74 rotates relative to the rotation station 1' due to inertia or the like according to the rotation force of the rotation station 1 '.

  Here, in Example 1 in which the set unit 2 is fixed to the rotation station 1, the liquids L <b> 0 to L <b> 2 in the chip cassette S <b> 2 of the set unit 2 remain even if the rotation station 1 is rotated at a non-discharge rotation speed. Even in the reaction area A1, there is a risk that the reaction area A1 is shifted to the outside in the direction in which the centrifugal force acts, and the reaction area A1 is shifted to a part in the circumferential direction. Therefore, in the reaction area A1, the spot 103 far from the center of rotation is more easily touched with a large amount of sample liquid L0, antibody reagent L2, etc. than the spot 103 near the center of rotation. Therefore, the reaction may vary between the spots 103.

  On the other hand, in the third embodiment, when the rotation station 1 ′ rotates, the set portion 2 ′ rotates relative to the rotation station 1 ′ due to inertia. In addition, the coil spring 76 is elastically deformed in accordance with the relative rotation of the rotating unit 74, and rotates the rotating unit 74 toward the reference position P11 during elastic recovery. Therefore, when rotating the rotation station 1 ′ at the non-discharge rotation speed, the set portion 2 ′ is relatively rotated so as to swing in the forward and reverse directions. Therefore, in the reaction area A1 of the chip cassette S2 of the third embodiment, the position where the liquid is offset easily changes compared to the case where the set portion 2 ′ is fixed. Therefore, the liquids L0 to L3 in the reaction area A1 are prevented from being shifted to a part in the circumferential direction. Therefore, in Example 3, it is suppressed that the reaction varies between the spots 103, and the inspection accuracy can be further improved as compared with the case where the set unit 2 is fixed to the rotating station.

In the third embodiment, the rotating unit 74 can be rotated relative to the rotating station 1 ′ even when the rotating station 1 ′ is rotated at the discharging rotation speed. Therefore, the liquids L0 to L3 discharged from the areas A1 and A2 are easily dispersed and discharged from the areas A1 and A2 in the circumferential direction. Therefore, compared with the case where the set part 2 is fixed to the rotation station, the discharged liquids L0 to L3 are easily absorbed directly by the water absorbent 112 in the entire circumferential direction.
In the third embodiment, when the rotation station 1 ′ stops at the positions P1 to P5 and the inertia or the like does not act on the rotation unit 74, the coil spring 76 is elastically restored to the natural length state. Therefore, the rotating unit 74 is moved and held at the reference position P11. Therefore, in the third embodiment, it is possible to return the rotating unit 74 to the reference position P11 without using an electric control member such as a motor. Therefore, for example, when the rotation station 1 ′ moves to the observation position P2, it is possible to image the spot 103 with the chip cassette S2 in the same direction as in the first embodiment.

Next, a description will be given of a fourth embodiment of the present invention. In the description of the fourth embodiment, components corresponding to the components of the first embodiment are denoted by the same reference numerals, and detailed description thereof is omitted. To do.
This embodiment is different from the first embodiment in the following points, but is configured in the same manner as the first embodiment in other points.

FIG. 24 is an explanatory diagram of a main part of the diagnostic system according to the fourth embodiment of the present invention.
In FIG. 24, in the diagnostic system S of the fourth embodiment, a plate-like temperature control mechanism 201 is disposed on the lower surface of the chip cassette S2. The temperature adjustment mechanism 201 includes a sheet-like heating element 202 and an electrode unit (not shown) that supplies power to the heating element 202. As the heating element 202, a sandwich structure in which a transparent high-resistance conductive polymer is sandwiched between transparent polyimide films can be employed. In addition, the heat generating body 202 can observe the chip cassette S2 from below by adopting a transparent configuration. The temperature control mechanism 201 is supplied with power from a power source (not shown) and can heat the liquid in the chip cassette S2.

  In addition, as a temperature control mechanism, it is not limited to the illustrated temperature control mechanism 201, Arbitrary temperature control mechanisms can be used. For example, a heating element is attached to the bottom surface of an aluminum block that matches the size of the substrate 101 of the chip cassette S2, and the heating aluminum block is brought into contact with the bottom surface of the substrate 101, thereby heating the solution in the chip cassette S2. A configuration in which the heat generating aluminum block is separated from the bottom surface of the substrate 101 when not heated can be conceived. Therefore, it is possible to observe the chip cassette S2 from below as in the configuration of the transparent heating element 202. In addition, it is also possible to utilize the effect of the residual heat according to the heat capacity of the aluminum block for assisting in heating.

Below the temperature control mechanism 201, a VCM (voice coil motor) 206 as an example of a vibration source for stirring liquid is disposed. The VCM 206 is in point contact with the bottom surface of the temperature adjustment mechanism 201, and is configured to be able to vibrate the chip cassette S2 in the vertical direction via the temperature adjustment mechanism 201. In the fourth embodiment, the VCM 206 and the temperature control mechanism 201 are configured to be able to contact and separate from the chip cassette S2. When the liquid in the chip cassette S2 is stirred, the VCM 206 and the temperature control mechanism 201 are in contact with the chip cassette S2. When stirring is completed, the chip cassette S2 is separated.
The VCM 206 and the temperature adjustment mechanism 201 can be arranged corresponding to the zero point position P1, but the present invention is not limited to this, and can be arranged at other positions P2 to P5. P1 to P5 It is also possible to arrange them at different positions.

  Further, the VCM 206 of the fourth embodiment stirs the liquid by periodically changing the frequency in a frequency region having a width including the resonance frequency of the secondary mode (bending + twisting mode) of the chip cassette S2. Therefore, in the fourth embodiment, the liquid inside the chip cassette S2 is not stirred by rotating the rotary station 1 as in the first embodiment, but is stirred using the VCM 206.

24, in the fourth embodiment, a reagent cartridge 211 is used in place of the nozzles 22 to 24 used in the first embodiment. The reagent cartridge 211 has a plurality of reagent containers 211a arranged side by side in a straight line, and each reagent container 211a contains (divides) a washing liquid, an antibody reagent, and a luminescent reagent by one batch. . In Example 4, a supply port 212 is formed at the lower end of each reagent container 211a as an example of a liquid container. In addition, the upper surface of each reagent container 211a is closed with a seal 213 as an example of a sealing member.
The reagent cartridge 211 of the fourth embodiment is configured such that the supply port of one of the reagent containers 211a is moved to a liquid supply position corresponding to the zero point position P1 of the first embodiment by a slider (not shown). The liquid supply position is not limited to the zero point position P1, can be changed to any position, and can be a position different from the VCM 206 or the like.

A liquid supply mechanism 221 is disposed above the reagent container 211a. The liquid supply mechanism 221 includes an injection needle 222 as an example of a supply member. A rubber hose 222a is connected to the injection needle 222, and the rubber hose 222a is connected to a pump (not shown). The injection needle 222 is supported by a slider 223, and the slider 223 is supported by an elevating mechanism 224 so as to be movable in the vertical direction.
Therefore, the liquid supply mechanism 221 can supply the liquid inside the reagent container 211a from the supply port 212 to the chip cassette S2 by injecting air from the pump while the injection needle 222 is lowered and penetrates the seal 213. It is configured.

(Operation of Example 4)
In the diagnostic system S of the fourth embodiment having the above-described configuration, unlike the first embodiment, the liquid in the chip cassette S2 is stirred by the VCM 206 and then drained by the rotation of the rotary station 1. At this time, the vibration generated from the VCM 206 periodically fluctuates in the frequency region including the resonance frequency of the second-order mode of the chip cassette S2, so that the vibration in the chip cassette S2 is larger than that in another frequency band. The liquid is stirred for a short time.
In addition, by using the reagent cartridge 211 without using the nozzles 22 to 24, the number of nozzles, pumps, etc. can be reduced, the configuration can be simplified and the cost can be reduced, and the amount for each time can not be subdivided. In comparison, weighing is unnecessary. Further, after use, the reagent cartridge 211 may be discarded, and the disposable configuration is obtained, which is safe for the operator and the like, and it is suppressed that the diagnosis result is adversely affected by contamination or the like.

(Example of change)
As mentioned above, although the Example of this invention was explained in full detail, this invention is not limited to the said Example, A various change is performed within the range of the summary of this invention described in the claim. It is possible. Modification examples (H01) to (H022) of the present invention are exemplified below.
(H01) In each of the above-described embodiments, the configuration in which the antigen is fixed to the spot 103 and the diagnosis is performed using the sample solution that can contain an antibody specific to the antigen is exemplified, but the present invention is not limited thereto. For example, in place of the antigen, nucleic acid, protein, antibody, ligand, receptor, etc. are fixed to the spot 103, and a test sample capable of interacting with the spot 103 is injected into the chip cassettes S2 and S2 ′. It is possible to make a diagnosis with
(H02) In each of the above-described embodiments, when supplying the cleaning liquid L1, it is desirable that the liquid is supplied from the reaction area A1 so that the liquid does not overflow. When the absorption capacity of the water absorbent 112 is large, a configuration in which the liquid overflows from the reaction area A1 to the drainage area A2 when supplying the cleaning liquid L1 is also possible.

(H03) In each of the above-described embodiments, the configuration in which the rotation station 1 is rotated using the stepping motor 6 is exemplified, but the present invention is not limited to this. For example, a configuration in which a DC motor is used as a drive source and the movement of the position of the rotation station 1 is controlled while detecting by a sensor or the like that the rotation station 1 moves to the positions P1 to P5 is also possible.
(H04) In each of the above embodiments, a configuration in which eight or more spots 103 are arranged is desirable, but it may be eight or less, and a configuration with only one spot 103 is possible.
(H05) In each of the above embodiments, the direction in which the camera 43 of the diagnostic device S1 captures images is illustrated from above, and the spot 103 is captured through the seal 113. However, the present invention is not limited to this. For example, a configuration in which the substrate 101 is made of a transparent member, a camera is installed below, an image is taken from below, and the spot 103 is imaged over the substrate 101 is also possible.

(H06) In each of the above embodiments, in the chip cassettes S2 and S2 ′, the configuration in which the reaction area A1, the drainage area A2, and the water absorbing agent 112 are arranged along the direction away from the rotation center 3 in the radial direction is exemplified. However, it is not limited to this. A configuration of a chip cassette in which the reaction area A1, the drainage area A2, and the water absorbing agent 112 are arranged along the direction in which the centrifugal force works is possible.
(H07) In each of the above-described embodiments, a configuration in which the water-absorbing agent 112 is disposed is desirable, but the present invention is not limited to this. For example, a configuration in which a drain shape is formed in the drainage area A2 to hold the drainage is also possible.
(H08) In each of the embodiments described above, the chip cassettes S2 and S2 ′ are exemplified by the configuration in which the inner wall 108 is provided and the water absorbing agent 112 is held in the holding space 109. However, the present invention is not limited to this. For example, the absorber is made of a material or material whose shape and position hardly change even when centrifugal force is applied, and the inner wall 108 of the chip cassette S2 ′ is omitted, and the absorber is exposed to the areas A1 and A2. A configuration in which it is arranged in a state is also possible.

(H09) In each of the above embodiments, the sample cassette L2 is supplied to the chip cassettes S2 and S2 ′ after being set in the setting units 2 and 2 ′. , S2 'is desirable because it is easy to stabilize the posture. However, the present invention is not limited to this, and a configuration in which the sample liquid L0 is supplied before the chip cassettes S2 and S2 ′ are set in the setting units 2 and 2 ′ is also possible.
(H010) In each of the above embodiments, ST4 and ST5 in the flowchart of the reaction observation process have exemplified the configuration in which the same cleaning process is executed. However, the present invention is not limited to this. For example, when the sample liquid L0 and the antibody reagent L2 are easily washed, the times T1 to T3 can be set to different times for ST4 and ST5, respectively. Similarly, in each process, even for the same process name, the time and the number of rotations can be set for each process according to the liquids L0 to L3.

(H011) In each of the above embodiments, the configuration in which the sample liquid L0 and the antibody reagent L2 are washed with one type of washing liquid L1 is exemplified, but the present invention is not limited to this. For example, when cleaning the sample liquid L0, a cleaning liquid according to the characteristics of the sample liquid L0 is supplied to the chip cassette S2 for cleaning. When cleaning the antibody reagent L2, the cleaning liquid according to the characteristics of the antibody reagent L2 is used. Can be supplied to the chip cassette S2 for cleaning. Moreover, when repeating washing | cleaning in multiple times, the structure which uses a different washing | cleaning liquid according to the frequency | count of washing | cleaning, such as using a different washing | cleaning liquid at the beginning and the last, is also possible. That is, the type of the cleaning liquid is not limited to one type, and a plurality of types of cleaning liquids can be used by sequentially changing them.
(H012) In each of the above embodiments, when supplying the cleaning liquid L0 and the reagents L2 and L3, the three nozzles 22 to 24 are used and the rotating station 1 is moved to the corresponding three positions P3 to P5. Although the configuration is exemplified, the configuration is not limited to this. For example, when a plurality of types of cleaning liquids are added or when a lot of reagents are necessary for the inspection, there is a configuration in which the rotation station 1 is moved to four or more positions corresponding to each using four or more nozzles. Is possible.

(H013) In each of the above embodiments, the personal computer PC has exemplified the configuration of a so-called tablet personal computer having the touch panel H2. However, the configuration is not limited to this, and a configuration using a desktop personal computer or a notebook personal computer is also possible. Further, the configuration is not limited to the personal computer PC, and a configuration in which the information processing apparatus is incorporated in the inspection apparatus S1 is also possible. Moreover, although the structure processed with one information processing apparatus was shown, the structure which has a control part for every apparatus is also possible. For example, the temperature control device 61 may be configured to be electrically disconnected from the computer main body H1, provided with a control unit independent of the personal computer PC, and operated independently from the personal computer PC.

(H014) In each of the embodiments described above, when the cleaning liquid L1 is drained, it is desirable to perform low-speed rotation. However, the present invention is not limited to this, and a configuration in which low-speed rotation is omitted is also possible.
(H015) In each of the above embodiments, when the luminescent reagent is drained, the configuration in which the medium speed rotation is omitted is illustrated, but the present invention is not limited to this, and it is also possible to perform the medium speed rotation.
(H016) In each of the above-described embodiments, the shape of the substrate 101 of the chip cassettes S2 and S2 ′ is a square configuration, but any shape such as a rectangle or an ellipse is possible. In addition, the configuration in which the reaction area A1 is configured in a circular shape is illustrated, but an elliptical shape, a rectangular shape, a square shape, or the like is also possible.
(H017) In each of the embodiments described above, as the turntable, a disk-like configuration like the rotation station 1 is desirable in that it can easily stabilize the center of gravity during rotation, but is not limited thereto. For example, it is possible to configure a turntable constituted by a bar member supported by the rotary shaft 3 and extending outward in the radial direction, and a set portion 2 provided at an outer end portion in the radial direction of the bar member. It is. In other words, the turntable is not limited to a disk shape as long as the chip cassettes S2 and S2 'are supported and can be rotated, and can have any shape.
(H018) In the above-described embodiments, the specific numerical values illustrated can be changed to arbitrary numerical values within the range where the operations and effects of the present invention are achieved.

(H019) In the first and second embodiments, the configuration in which the microheater 63 of the temperature control mechanism 61 is fixedly disposed below the rotation station 1 is exemplified. However, the present invention is not limited to this. A configuration in which the heater 63 is incorporated in the rotary station 1 is also possible. In the third embodiment, a configuration in which the micro heater 63 is incorporated in the rotating unit 74 is also possible.
(H020) In each of the above embodiments, the configuration in which the diagnostic system S has one personal computer PC is exemplified, but the present invention is not limited to this, and the diagnostic system S may have a plurality of information processing apparatuses. That is, a configuration in which information is transmitted to and received from another information processing apparatus using the communication function of the computer main body H1 of the personal computer PC can be applied to the diagnostic system S. For example, a configuration in which the computer main body H1 transmits the measurement result to a remote information processing apparatus via the Internet as an example of a communication line is possible. As a result, for example, it is possible to request a second opinion or the like from another specialist in a remote place. In addition, a plurality of inspection apparatuses S1 and a personal computer PC can be connected via a LAN: Local Area Network as an example of a communication line, and measurement results inspected by each inspection apparatus S1 can be integrated and used. . Therefore, for example, the measurement result can be statistically processed to correct the analysis method for the imaging data.

(H021) In each of the above embodiments, the diagnosis system S has exemplified the configuration in which one personal computer PC executes the reaction observation process. However, the present invention is not limited to this. Is possible. For example, the function of the image analysis means C11 is given to an information processing apparatus installed in a remote place, not the personal computer PC that controls the inspection apparatuses S1 and S1 ′. Further, the image data captured by the inspection devices S1 and S1 ′ is transmitted from the personal computer PC to the remote information processing device. The remote information processing apparatus is configured to analyze the received image data and send the analyzed measurement result to the personal computer PC. The personal computer PC can be configured to display the received measurement results on the display panel H2.
(H022) In each of the above embodiments, the configuration in which the camera 43 reads the barcode is illustrated, but the present invention is not limited to this. For example, a barcode reader as an example of an identifier reading member is connected to the personal computer PC connected to the diagnostic devices S1 and S1 ′, and the barcodes of the chip cassettes S2 and S2 ′ are read using the barcode reader. It is also possible.

  The test system, test method, and test substrate according to the present invention, for example, using a test substrate in which antigens of different types of biomolecules are fixed as a plurality of spots, a sample to be analyzed can be obtained at a high speed with a small amount of sample, Inexpensive, safe and easy to handle, it can analyze multiple items at the same time, and can be applied to point-of-care test analysis for use in clinical settings, etc. with a compact footprint.

1, 1 '... turntable,
3, 3 '... center of rotation,
4 ... Rotation drive mechanism,
22 ... Supply part of cleaning liquid,
43. Observation member,
74: Second turntable,
102,102 '... separation part,
102a '... inclined surface,
102b '... the wall,
103 ... Spot,
112 ... Absorber,
113, 113 '... covering member,
113a, 113a '... supply port,
A1 ... accommodating part,
A2 ... Drainage part,
C2: Control means for draining cleaning liquid,
L0 ... Inspection sample, liquid,
L1: Cleaning liquid, liquid,
N1 ... non-discharge rotation speed,
N2, N3 ... rotational speed for discharge,
S ... Inspection system,
S1, S1 '... inspection device,
S2, S2 '... inspection substrate.

Claims (10)

  1. A turntable rotatable around the center of rotation;
    An inspection base supported by the turntable, wherein the detection target is a storage unit that can store a liquid test sample, and the detection target is disposed in the storage unit and the test sample contains a component to be detected A spot for fixing a component that reacts with the component, a drainage portion disposed radially outside the storage portion with respect to the rotation center, and a separation that separates the storage portion and the drainage portion An inspection base having a portion;
    A rotational drive mechanism for rotationally driving the rotary table;
    A cleaning liquid supply section for supplying a cleaning liquid to the housing section of the inspection substrate;
    When the cleaning liquid is supplied via the rotational drive mechanism, the liquid is discharged from the liquid by rotating the turntable at a rotational speed at which centrifugal force is applied to move the liquid from the container to the liquid drain. Means for controlling the drainage of the cleaning liquid to be moved to the unit,
    An observation member for observing the spot of the container when the cleaning liquid is drained from the container;
    An inspection system characterized by comprising:
  2. An absorber that absorbs the liquid that has been disposed in the drainage section and has moved to the drainage section;
    The inspection system according to claim 1, further comprising:
  3. A transparent coating member that covers the storage unit and the drainage unit from above, and a supply port that is formed in the coating member and that is supplied with a liquid test sample and cleaning liquid, and when viewed from above, The inspection base having the supply port provided at a position corresponding to the accommodating portion and non-overlapping in a spot;
    The observation member disposed above the turntable;
    The inspection system according to claim 1, further comprising:
  4. The separation unit having an inclined surface that is inclined upward in the direction of gravity toward the drainage unit from the storage unit, and a standing wall-like wall portion provided on the drainage unit side of the inclined surface,
    The inspection system according to claim 1, further comprising:
  5. When the cleaning liquid is supplied, the liquid is allowed to flow in the storage unit by rotating the turntable at a non-discharge rotational speed at which a centrifugal force capable of retaining the liquid in the storage unit is applied. A control means for controlling the drainage of the cleaning liquid, which rotates the rotating table at the rotational speed for discharging on which a centrifugal force that moves from the containing section to the draining section acts;
    The inspection system according to claim 1, further comprising:
  6. A second turntable that supports the inspection substrate and is rotatably supported by the turntable;
    The inspection system according to claim 1, further comprising:
  7. A vibration source that contacts the inspection substrate and applies vibration to the inspection substrate to agitate the liquid in the container;
    The inspection system according to claim 1, further comprising:
  8. The cleaning liquid supply unit and the reagent supply unit configured by a cartridge having a plurality of liquid containers in which the liquid supplied to the storage unit of the test substrate is stored in small portions;
    The inspection system according to claim 1, further comprising:
  9. A container capable of accommodating a liquid test sample, and a spot that is disposed in the container and in which a component that reacts with the component to be detected when the test sample contains a component to be detected is fixed; The inspection substrate having a drainage part arranged adjacent to the accommodation part and a separation part for separating the accommodation part and the drainage part is provided on a turntable that can rotate around a rotation center. A step of disposing the drainage part on the outer side in the radial direction with respect to the center of rotation than the accommodating part and supporting the turntable;
    Supplying an inspection sample to the inspection substrate;
    Supplying a cleaning liquid to the housing portion of the inspection substrate;
    When the cleaning liquid is supplied, the liquid discharging step of moving the liquid to the liquid discharging part by rotating the turntable at a rotational speed at which centrifugal force is applied to move the liquid from the containing part to the liquid discharging part. When,
    A step of observing the spot of the container when the cleaning liquid is drained from the container;
    The inspection method characterized by performing.
  10. A rotating table that is rotatable about the rotation center and rotated when the liquid is drained, a supply unit that supplies the cleaning liquid, an observation member that is observed when the liquid test sample and the cleaning liquid are drained, An inspection substrate used in an inspection apparatus and supported by the turntable,
    A container capable of accommodating a liquid test sample;
    A spot in which a component that reacts with the component to be detected is fixed when the component to be detected is included in the test sample,
    A drainage part that is disposed radially outside the storage part with respect to the rotation center of the turntable, and that drains liquid from the storage part when the turntable rotates;
    A separation unit that separates the storage unit and the drainage unit;
    An inspection substrate comprising:
JP2015104817A 2014-05-26 2015-05-22 Inspection system, inspection method, and inspection base Pending JP2016006414A (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP2014108536 2014-05-26
JP2014108536 2014-05-26
JP2015104817A JP2016006414A (en) 2014-05-26 2015-05-22 Inspection system, inspection method, and inspection base

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP2015104817A JP2016006414A (en) 2014-05-26 2015-05-22 Inspection system, inspection method, and inspection base

Publications (1)

Publication Number Publication Date
JP2016006414A true JP2016006414A (en) 2016-01-14

Family

ID=55224920

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2015104817A Pending JP2016006414A (en) 2014-05-26 2015-05-22 Inspection system, inspection method, and inspection base

Country Status (1)

Country Link
JP (1) JP2016006414A (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101870951B1 (en) * 2016-07-11 2018-06-25 올텍오토메이션(주) Precision Positioning Vibrator using Voice Coil Linear Motor
JP6434114B1 (en) * 2017-11-30 2018-12-05 シスメックス株式会社 Measuring method and measuring device

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005257337A (en) * 2004-03-09 2005-09-22 Brother Ind Ltd Inspection object receiver, inspection device, and inspection method
JP2011013000A (en) * 2009-06-30 2011-01-20 Consonal Biotechnologies Co Ltd Method for analyzing biochip, and system for automatic analysis of the same
JP2011524016A (en) * 2008-06-09 2011-08-25 エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft Systems and methods for hybridization slide processing

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005257337A (en) * 2004-03-09 2005-09-22 Brother Ind Ltd Inspection object receiver, inspection device, and inspection method
JP2011524016A (en) * 2008-06-09 2011-08-25 エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft Systems and methods for hybridization slide processing
JP2011013000A (en) * 2009-06-30 2011-01-20 Consonal Biotechnologies Co Ltd Method for analyzing biochip, and system for automatic analysis of the same

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101870951B1 (en) * 2016-07-11 2018-06-25 올텍오토메이션(주) Precision Positioning Vibrator using Voice Coil Linear Motor
JP6434114B1 (en) * 2017-11-30 2018-12-05 シスメックス株式会社 Measuring method and measuring device

Similar Documents

Publication Publication Date Title
AU625064B2 (en) Test card for performing assays
Feng et al. Immunochromatographic diagnostic test analysis using Google Glass
ES2271941T3 (en) Automatic analysis method with continuous and random access.
EP1205756B1 (en) Automated liquid level sensing system and method
DE60213873T2 (en) Stackable sample tray assembly
JP4221083B2 (en) Image analysis method and apparatus
KR20140082756A (en) Systems and methods for multi-analysis
AU2010282784B2 (en) Methods and apparatus for ascertaining interferents and physical dimensions in liquid samples and containers to be analyzed by a clinical analyzer
CA2132960C (en) Automated continuous and random access analytical system and components thereof
AU2008234977B2 (en) Automated multi-detector analyzer
KR102005597B1 (en) Portable rapid diagnostic test reader
St John et al. Existing and emerging technologies for point-of-care testing
US6190617B1 (en) Sample container segment assembly
US5096670A (en) Automated patient sample analysis instrument
CN102116771B (en) Automatic enzyme-linked immune analysis analyzer
CN102482702B (en) Diagnostic device and methods involving
US20120071342A1 (en) System and method for detecting multiple molecules in one assay
US20110245061A1 (en) Automated Sample Workcell and Method of Operation
Wilson et al. The Simoa HD-1 analyzer: a novel fully automated digital immunoassay analyzer with single-molecule sensitivity and multiplexing
KR101579327B1 (en) Modular point-of-care devices and uses thereof
US8840838B2 (en) Centrifuge configurations
JP2007501415A (en) Apparatus and method for process monitoring
US20170283845A1 (en) Systems and methods for multi-purpose analysis
US10371710B2 (en) Systems and methods for fluid and component handling
US10018643B2 (en) Systems and methods for multi-analysis

Legal Events

Date Code Title Description
A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20150611

A711 Notification of change in applicant

Free format text: JAPANESE INTERMEDIATE CODE: A711

Effective date: 20180219

A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20180227

A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A821

Effective date: 20180219

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20180327

A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A821

Effective date: 20180327

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20181220

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20190108

A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20190311

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20190716

A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20190911

A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20191203

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20191204