Inspection Equipment

Abstract

To move an inspection container stably, and to properly put the inspection container in contact with a temperature adjustment unit on an inspection table with the temperature adjustment unit thereon not displaced or inclined.SOLUTION: The present invention relates to an inspection device that is configured to make an inspection container 2 having a storage unit 11 storing an inspected liquid formed sequentially move to a temperature adjustment unit composed of a plurality of temperature adjustment stations S1 to S3 arranged on a common periphery on an inspection table 5 and make the inspection container contact with the temperature adjustment unit. The inspection device comprises: a rotation supporting body 21 that is rotated on the inspection table 5 by a rotation shaft 23a, and causes the inspection container 2 to move to the plurality of temperature adjustment stations S1 to S3, supporting the inspection container; and shaft direction movement means 24 that causes the rotation supporting body 21 to move in a shaft direction with respect to the rotation shaft 23a. The shaft direction movement means 24 is configured to cause the rotation supporting body 21 to be located in a contact position where the inspection container 2 contacts with the temperature adjustment unit, and in a separate position where the inspection container 2 separates from the temperature adjustment unit.SELECTED DRAWING: Figure 9

Description

[Technical field]

[0001] The present invention relates to an inspection device, and more particularly to an inspection device in which an inspection container having a storage section for storing a test liquid is sequentially moved and brought into contact with a plurality of temperature control sections arranged on a common circumference. [Background technology]

[0002] Conventionally, testing for viral infections involves genetic analysis, in which sequence information of nucleic acid molecules extracted from specimens (biological samples) such as nasopharyngeal swabs, sputum, and saliva is analyzed. In this method, PCR (Polymerase Chain Reaction) is used, in which the nucleic acid molecules contained in the test liquid containing the specimen are amplified by sequentially subjecting them to thermal denaturation, hybridization, and extension reactions. In order to cause each of the above-mentioned thermal denaturation, hybridization, and extension reactions to occur, the test liquid containing the above-mentioned nucleic acid molecules must be adjusted to the required temperature at which each of the above-mentioned reactions occurs, and in order to obtain the amount of amplification product required for the test, the above-mentioned reactions must be repeated several dozen cycles. A known example of an inspection device equipped with such a temperature control unit is an inspection device in which an inspection container having a storage section for storing the test liquid is moved sequentially to and brought into contact with multiple temperature control units arranged on a common circumference (Patent Document 1). In Patent Document 1, the test container has a disk shape and includes a motor for rotating the test container. In Patent Document 1, the test container together with the motor is moved in the axial direction of the rotation shaft of the motor, so that the container part containing the test liquid of the disk-shaped test container comes into contact with the temperature control part, and when the test container is rotated, the test container together with the motor is moved in the axial direction of the rotation shaft to be separated from the temperature control part. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Patent No. 4626891 Summary of the Invention [Problem to be solved by the invention]

[0004] However, in the inspection device of Patent Document 1, the axial movement of the inspection container is achieved by moving the motor together with the inspection container. However, when the motor is moved, there is a risk that the position of the rotation axis may shift or tilt, and there is a problem that the container holding portion of the inspection container cannot be properly brought into contact with the temperature adjustment portion, making this impractical. In view of the above problems, the present invention provides an inspection device that can stably move an inspection container and properly contact the temperature adjustment unit without shifting or tilting. [Means for solving the problem]

[0005] That is, the testing device according to the invention of claim 1 is a testing device in which a test container having a container portion for accommodating a test liquid is moved in sequence to contact with a plurality of temperature control units arranged on a common circumference, a rotating shaft that rotates at the center of a circumference on which the plurality of temperature control units are arranged, a rotating support that is rotated by the rotating shaft to support the cuvette and move it to the plurality of temperature control units, and an axial movement means that moves the rotating support in the axial direction relative to the rotating shaft, The rotating support supports an end of the test vessel so that the bottom of the test vessel is in contact with the temperature control unit, When positioning the inspection vessel in the temperature adjustment section, the axial movement means positions the rotating support at a contact position where the inspection vessel contacts the temperature adjustment section, and when moving the inspection vessel from the temperature adjustment section, the axial movement means positions the rotating support at a separated position where the inspection vessel is separated from the temperature adjustment section. Effect of the Invention

[0006] The inspection device of the present invention comprises a rotating shaft that rotates at the center of a circumference on which a plurality of temperature control units are arranged, a rotating support that is rotated by the rotating shaft to support the inspection vessel and move it to the plurality of temperature control units, and an axial movement means for moving the rotating support axially relative to the rotating shaft, and the axial movement means moves the rotating support axially relative to the rotating shaft to position the inspection vessel at a contact position where it contacts the temperature control unit and at a separated position where it is separated from the temperature control unit. That is, since the axial movement means moves the rotary support in the axial direction relative to the rotary shaft, the cuvette can be stably moved and appropriately brought into contact with the temperature adjustment unit. [Brief description of the drawings]

[0007] [Figure 1] Cross-sectional view of the PCR testing device according to this embodiment. [Diagram 2] A plan view illustrating the inspection table and each station. [Diagram 3] Plan view of the test container [Figure 4] Cross-sectional view of the IV-IV portion in FIG. [Diagram 5] A diagram explaining how to use the test container [Figure 6] Diagram explaining the structure of a means of transportation [Figure 7] Plan view of the rotating support [Figure 8] Cross-sectional view of a PCR testing device when the rotating support is in the contact position [Figure 9] Cross-sectional view of a PCR testing device when the rotating support is in the separated position DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] The illustrated embodiment will now be described. FIG. 1 shows a cross-sectional view of a PCR testing device 1, which performs a so-called PCR (Polymerase Chain Reaction) test on a sample collected from a patient to determine whether or not the patient is infected with a virus. The contents of the PCR test are well known and therefore will not be described in detail, but the test involves amplifying nucleic acid molecules extracted from specimens (biological samples) such as nasopharyngeal swabs, sputum, saliva, etc. collected from a patient, analyzing the sequence information, and testing whether or not the patient is infected with a virus. The PCR testing device 1 of this embodiment uses a real-time PCR method that monitors the amplified products in real time. In order to amplify a nucleic acid molecule by PCR, the nucleic acid molecule must be subjected to successive thermal denaturation, hybridization, and extension reactions. To achieve this, the test solution must be continuously adjusted to a different temperature for each reaction. Once the PCR procedure has yielded the amount of amplification product required for analysis, the test liquid can be irradiated with excitation light of a specific wavelength and the emitted fluorescence detected to perform real-time analysis and identify viral infection. In particular, the PCR testing device 1 of this embodiment is a so-called multiplex PCR testing device that can simultaneously detect influenza types A and B, as well as coronavirus (SARS-CoV-2), by detecting different fluorescent reactions.

[0009] In order to perform a PCR test using the PCR testing device 1 of this embodiment, first the test liquid containing a specimen such as a nasopharyngeal swab, sputum, saliva, etc. collected from a patient is placed in the test container 2, which is then set in the PCR testing device 1. The PCR testing device 1 comprises a bottomed box-shaped housing 3 that is open at the top, a lid 4 that is attached to the top of the housing 3 via a hinge so as to be able to be opened and closed, a test table 5 that is arranged to cover the open upper portion of the housing 3, a moving means 6 that moves the test container 2 above the test table 5, a plurality of temperature adjustment means 7 that cause each of the above-mentioned reactions, and a fluorescence detection means 8 that detects fluorescence, all of which are controlled by a control means 9 provided inside the housing 3. In this way, the PCR testing device 1 of this embodiment is configured compactly and is easy to use even in small medical institutions such as clinics. In this embodiment, the moving means 6 is configured to move the test container 2 in a circumferential direction, and moves it to each station shown as S1 to S4 arranged on a common circumference on the test table 5 as shown in Figure 2. In this embodiment, from the top of FIG. 2 clockwise, there are a heating station S1 that causes thermal denaturation, an annealing station S2 that causes hybridization, a temperature-raising station S3 that causes an extension reaction, and an inspection station S4 that performs the above-mentioned fluorescence detection, and among these, the temperature control stations S1 to S3 are configured as multiple temperature control units.

[0010] Next, regarding the above-mentioned test container 2, FIG. 3 is a plan view of the above-mentioned test container 2, FIG. 4 is an enlarged cross-sectional view of portion IV-IV of the test container 2 in FIG. 3, and FIG. 5 is a diagram explaining how to use the test container 2. The test container 2 has multiple storage sections 11 (eight in this embodiment) formed therein for storing the test liquid, and each storage section 11 is capable of storing the test liquid including a biological sample collected from a different patient. The test container 2 is moved by the moving means 6 along a circular path between each of the stations S1 to S4, and therefore the test container 2 has an elongated curved shape in a planar view, and the storage sections 11 are formed in a state where they are aligned in a row along the curved shape.

[0011] As shown in Figure 4, the testing container 2 is composed of a main body 12 in which the above-mentioned storage section 11 is formed, a transparent resin sheet 13 fixed to the back surface of the main body 12, and a cover film 14 attached to the surface of the main body 12. The main body 12 is made of a hard resin and is transparent enough to visually confirm the storage section 11 formed inside. The main body 12 has a curved shape in a plan view, and the arc shape on the outer periphery forming the long side of the main body 12 is shaped to match the outer periphery of the rotating support 21 constituting the moving means 6 (see FIG. 7). In addition, support pieces 15 for supporting the test container 2 on the rotating support 21 are provided at both ends of the main body 12, which are in front and behind the movement direction of the test container 2, and the support pieces 15 are provided at a position biased upward relative to the main body 12 as shown in Figure 5, and the test container 2 is supported by the support pieces 15 being supported from below by the rotating support 21. Further, an engagement hole 15a is formed in each of the support pieces 15 for positioning with respect to the rotary support 21, and the engagement hole 15a of one of the support pieces 15 is an elongated hole to absorb dimensional errors during manufacturing.

[0012] In Figure 4, a recess that constitutes the storage section 11 is formed on the back side of the main body section 12, and by covering the entire back side of the main body section 12 with the transparent sheet 13, the recess is closed and the storage section 11 is formed. Further, a test area 11a having a substantially circular shape in a plan view is formed in the container 11, and a minute amount of test liquid is accommodated in the test area 11a. In addition, protrusions 11b that form upper and lower passages in the radial direction front and rear of the rotating support 21 that supports the test container 2 are formed from each testing area 11a, and an inlet 16 and an outlet 17 that communicate with each protrusion 11b are opened on the surface of the main body 12. A minute amount of the test liquid is injected from the injection port 16 using a micropipette, and air pushed out by the test liquid that has flowed into the test area 11a is discharged from the discharge port 17. The injection port 16 and the outlet port 17 have the same shape, and either one can be used as the injection port 16. In order to facilitate injection using a micropipette, the openings of the injection port 16 and the outlet port 17 are formed with tapered surfaces. In this embodiment, the back side of the test container 2 is covered with a transparent sheet 13, and the inlet 16 and outlet 17 are connected to the protrusions 11b at both ends of the test area 11a. As a result, excitation light can be irradiated onto the test area 11a from the back side of the test container 2 in the test station S4, and the fluorescence emitted by the test liquid can be received at the back side of the test container 2.

[0013] The cover film 14 is provided to prevent leakage of the test liquid contained in the storage section 11 and evaporation of the test liquid due to heating, and covers almost the entire surface of the test liquid main body section 12. The cover film 14 has an adhesive surface, and after a medical professional injects the test liquid into the storage section 11, the cover film 14 is attached to the surface of the main body section 12 to seal the injection port 16 and the discharge port 17.

[0014] Next, each part of the PCR testing device 1 will be described. As shown in FIG. 1, a touch panel 3a connected to the control means 9 is provided on the front surface of the housing 3, making it possible to check the operating status of the PCR testing device 1 and perform required operations. The lid portion 4 is supported via a hinge on the rear side of the PCR testing device 1 relative to the front side of the housing 3, and is designed to open and close the top of the housing 3 and, when opened, to open the front side of the housing 3. When performing a PCR test, the lid portion 4 is closed, and the inner lid 22, which is provided on the inside of the lid portion 4 and will be described later, comes into contact with the rotating support 21 of the moving means 6 and the supported test container 2.

[0015] The inspection table 5 is a plate-like member provided to cover the upper open portion of the housing 3, and has an opening 5a formed in the center as shown in FIG. 2. The inspection table 5 is capable of transmitting drive power by connecting a rotating shaft 23a of a driving means 23 arranged within the housing 3 to a rotating support 21 located above the inspection table 5. Surrounding the central opening 5a are temperature control stations for performing PCR, including a heating station S1 that causes thermal denaturation, an annealing station S2 that causes hybridization, and a temperature-raising station S3 that causes an extension reaction.In addition, between the heating station S1 and the temperature-raising station S3, an inspection station S4 that performs fluorescence detection is located on a common circumference centered on the rotation axis 23a. In this embodiment, the inspection station S 4 is located at the front of the housing 3 .

[0016] Next, the moving means 6 will be described with reference to Fig. 6. The moving means 6 includes a driving means 23 fixed to the underside of the inspection table 5, and a substantially disk-shaped rotating support 21 rotatably provided above the inspection table 5, and the rotating support 21 is provided so as to be movable forward and backward in the axial direction relative to a rotating shaft 23a of the driving means 23. The moving means 6 includes an axial moving means 24 for moving the rotating support 21 forward and backward in the axial direction relative to the rotating shaft 23a of the driving means 23. The driving means 23 uses a servo motor, a stepping motor, or the like, and the rotating support 21 can be rotated under the control of the control means 9, so that the inspection container 2 supported by the rotating support 21 can be positioned at the required temperature control station S1 to S3. 7, the rotary support 21 has a substantially disk shape, and is provided at its center with a boss 21a as a coupling member coupled with the rotary shaft 23a of the driving means 23. Also, an annular flat plate portion 21b for supporting the cuvette 2 is formed at its outer periphery. Further, a circular rib 21c is formed on the rear surface of the rotary support 21 so as to protrude downward, and an origin detection means 25 is provided on the inspection table 5 in response to this. This origin detection means 25 detects a marker indicating the origin position formed on the rib 21c of the rotating support 21, and based on this, recognizes the movement position in the rotational direction of the test container 2 supported by the rotating support 21, making it possible to accurately stop the test container 2 at the temperature control stations S1 to S3.

[0017] The annular flat plate portion 21b formed on the outer periphery of the rotating support 21 is formed by a flat surface having a width dimension almost the same as the width direction relative to the longitudinal direction of the cuvette 2. The rotating support 21 has a notch portion 21g formed on the outer periphery to support the cuvette 2, and the annular flat plate portion 21b is divided so that the main body portion 12 of the cuvette 2 is accommodated in the divided portion. When the test vessel 2 is accommodated in the annular flat portion 21b, a ring is formed, and the arc shape of the outer peripheral edge of the annular flat portion 21b is smoothly continuous with the arc shape on the outer periphery of the test vessel 2, so that a disk shape is obtained by the supported test vessel 2 and the rotating support 21. Furthermore, support pins 21d that engage with engagement holes 15a formed in the support piece 15 of the test container 2 are erected on both divided ends of the annular flat portion 21b that support the support piece 15, and by engaging the engagement holes 15a of the test container 2 with the support pins 21d of the rotating support 21, medical personnel can support both ends of the test container 2 on the rotating support 21 and set the test container 2 containing the test liquid in the PCR testing device 1. The thicknesses of the main body 12 of the test container 2 supported by the rotating support 21 are set so that the upper surface of the main body 12 is positioned above the upper surface of the annular flat plate portion 21b, and the lower surface of the main body 12 is positioned below the lower surface of the annular flat plate portion 21b, thereby ensuring that the bottom of the test container 2 is in contact with each of the temperature control stations S1 to S3. In addition, the annular flat portion 21b is provided with an abutment portion 21e formed at the same height as the upper surface of the test vessel 2 supported by the rotating support 21, at a position opposite the divided portion that accommodates the main body portion 12 of the test vessel 2, sandwiching the boss 21a. The shape of the rotating support 21 is not limited to a disk shape, and it can be other shapes such as a sector shape or an X shape as long as it is rotated by the rotating shaft 23a to support the cuvette 2 for rotational movement and has a configuration that allows it to move axially back and forth relative to the rotating shaft 23a.

[0018] Regarding the axial movement means 24, the rotating shaft 23a of the driving means 23 and the boss 21a of the rotating support 21 are connected by a spline joint, which transmits the rotation of the rotating shaft 23a to the rotating support 21 and allows the rotating support 21 to move in the axial direction relative to the rotating shaft 23a. 6, a ring-shaped cam 21f is formed on the lower surface of the rotary support 21 so as to protrude downward, and the opening 5a of the inspection table 5 is formed so as not to interfere with the cam 21f. A cam follower 26 is fixed to the rear surface of the inspection table 5 so as to be located inside the opening 5a. When the cam 21f comes into contact with the cam follower 26 from above and the boss 21a of the rotary support 21 and the rotary shaft 23a are engaged with each other, the rotary support 21 is supported by the cam follower 26 from below. The rotating support 21 moves axially relative to the rotating shaft 23a in accordance with the changing protrusion amount of the cam 21f, and rises and falls relative to the inspection table 5. In this embodiment, the cam 21f and the cam follower 26 form an axial movement means 24.

[0019] When the test container 2 is located at the heating station S1, the annealing station S2, or the temperature-raising station S3, the rotating support 21 descends as the protrusion amount of the cam 21f that contacts the cam follower 26 decreases, and is positioned at the contact position as shown in Figure 8. At this time, the inspection container 2 supported by the rotating support 21 is pressed from above by the inner lid 22 provided on the inside of the lid portion 4, as described below, so that when it stops at each of the temperature control stations S1 to S3, the inspection container 2 is pressed against the temperature control block 32 of the temperature adjustment means 7 provided in each of the temperature control stations S1 to S3. On the other hand, when the inspection container 2 moves to a position other than each of the temperature control stations S1 to S3, i.e., other positions including the inspection station S4, the rotating support 21 rises as the protrusion amount of the cam 21f contacting the cam follower 26 increases, and the rotating support 21 is positioned at a distance as shown in Figure 9, so that the undersides of the inspection container 2 and the rotating support 21 are separated from the surface of the inspection table 5 and the temperature control block 32 to prevent them from coming into contact with each other. In this way, by positioning the rotating support 21 at the contact position when the test container 2 is located at each temperature control station S1 to S3, the bottom of the test container 2 can be pressed against the temperature control block 32, and the lower surface of the test container 2 can be reliably brought into contact with the temperature control block 32, making it possible to accurately and quickly adjust the temperature of the test liquid. On the other hand, at other positions, the rotating support 21 is positioned at a distance so that the underside of the test container 2 does not come into contact with the inspection table 5 and the surface of the transparent sheet 13 that forms the bottom of the test container 2 is not damaged, thereby preventing the irradiation of excitation light and the detection of fluorescence at the inspection station S4 from being hindered.

[0020] An inner lid 22 provided on the inside of the lid portion 4 for pressing the cuvette 2 is formed in a disk shape and is rotatably supported by a support shaft 4a provided in the approximate center of the lid portion 4. The support shaft 4a is arranged to be positioned coaxially with the rotation shaft 23a of the driving means 23 when the lid portion 4 is closed, and when the lid portion 4 is closed, the inner lid 22 presses the rotating support 21 and the inspection container 2, so that the rotating support 21, the inspection container 2 and the inner lid 22 rotate integrally around the same center. The inner lid 22 is supported so as to be suspended from the support shaft 4a so as to be movable in the axial direction, and a spring 27 is elastically mounted between the inner lid 22 and the lid portion 4. This biases the inner lid 22 in a direction away from the lid portion 4, so that when the lid portion 4 is closed, it presses the rotating support 21 downward toward the inspection table 5 and absorbs the load in the direction approaching the lid portion 4.

[0021] As shown in Figure 1, an annular outer abutment portion 22a and an inner abutment portion 22b are formed on the lower surface of the outer peripheral edge of the inner lid 22, and when the lid portion 4 is closed, it abuts from above against the test container 2 supported by the rotating support 21 and the abutment portion 21e formed on the rotating support 21. In other words, when the lid portion 4 is closed, the outer abutment portion 22a and the inner abutment portion 22b abut against the test container 2 supported by the rotating support 21 and the abutment portion 21e provided at the opposing position, thereby making it possible for the inner lid 22 to press the rotating support 21 and the abutment portion 21e in a balanced manner. Here, the distance between the outer abutment portion 22a and the inner abutment portion 22b is set slightly wider than the width of the support piece 15 provided at both the front and rear ends of the testing container 2, so that when the outer abutment portion 22a and the inner abutment portion 22b abut against the upper surface of the testing container 2, the support piece 15 is positioned between the outer abutment portion 22a and the inner abutment portion 22b. Furthermore, the inspection area 11a set in the storage section 11 of the above-mentioned inspection container 2 is also positioned between the outer abutment portion 22a and the inner abutment portion 22b, so that even if the atmosphere inside the storage section 11 expands due to heating and the cover film 14 covering the inspection area 11a expands, this can be tolerated.

[0022] When the rotating support 21 is positioned at the contact position shown in Figure 8 by the cam 21f, the spring 27 biases the inspection container 2, whose inner lid 22 is supported by the rotating support 21, against the rotating support 21 via the support pieces 15 at both ends, and presses it against the temperature control blocks 32 of each temperature control station S1 to S3 provided on the inspection table 5. In contrast, when the rotating support 21 is positioned at the separated position shown in Figure 9 by the cam 21f, the axial moving means 24 raises the rotating support 21 against the biasing force of the spring 27, so that the inner lid 22 presses the inspection container 2 and biases it against the rotating support 21, while separating it from the temperature control block 32 and the inspection table 5. As a result, the cuvette 2 is always pressed against the inner lid 22, and therefore does not float up from the rotary support 21 and come off the support pin 21d during movement, and can be moved in a stable state.

[0023] Next, the temperature adjustment means 7 provided in the heating station S1, the annealing station S2, and the temperature-raising station S3 will be described. Here, the temperature adjustment means 7 in the annealing station S2 will be described with reference to Fig. 6, but the temperature adjustment means 7 in the heating station S1 and the temperature-raising station S3 also have a basically similar configuration. The temperature control means 7 is composed of a temperature control block 32 whose upper surface is arranged to protrude from the upper surface of the inspection table 5, a Peltier element 31 as a thermoelectric element whose upper surface is in contact with the temperature control block 32 and controls the temperature of the temperature control block 32, a heat sink 33 arranged in contact with the lower surface of the Peltier element 31 on the temperature control block 32, and a temperature measurement means 34 for measuring the temperature of the temperature control block 32. The temperature control block 32 is made of aluminum, which has a relatively high thermal conductivity. Since the Peltier element 31 is well known, detailed explanation will be omitted, but the temperature control block 32 on one side in contact with the Peltier element 31 is heated by a current applied by the control means 9, and heat is absorbed by the heat sink 33 in contact with the other side.

[0024] Here, the temperature adjustment means 7 constituting the heating station S1 and the temperature increasing station S3 in this embodiment has four temperature adjustment blocks 32 as shown in Figure 2, and each of the temperature adjustment blocks 32 is provided with the Peltier element 31 and the heat sink 33. The four temperature control blocks 32 are arranged along the circumferential movement path of the inspection container 2 which moves in the rotational direction of the rotating support 21, and when the inspection container 2 stops at the heating station S1 and the temperature raising station S3, one temperature control block 32 abuts against each of the eight storage sections 11 formed in the inspection container 2, with each two storage sections 11 corresponding to one another. In other words, in the heating station S1 and the temperature increasing station S3, the temperature of the test liquid contained in the two containers 11 is adjusted by a temperature adjustment means 7 consisting of a set of a Peltier element 31, a temperature control block 32, a heat sink 33, and a temperature measurement means 34.

[0025] In contrast, in this embodiment, the temperature adjustment means 7 constituting the annealing station S2 has eight temperature adjustment blocks 32 as shown in Figure 2, and each temperature adjustment block 32 is provided with the Peltier element 31, heat sink 33, and temperature measurement means 34. As a result, when the test vessel 2 stops at the annealing station S2, each of the eight storage sections 11 formed in the test vessel 2 abuts against one temperature control block 32. In other words, in the annealing station S2, a temperature control means 7 consisting of a set of a Peltier element 31, a temperature control block 32, a heat sink 33, and a temperature measurement means 34 corresponds to each storage section 11, making it possible to individually adjust the temperature of the test liquid in each storage section 11.

[0026] The temperature measuring means 34 measures the temperature of the temperature control block 32, i.e., the temperature of the part in contact with the test vessel 2, and the measured temperature is transmitted to the control means 9. The control means 9, acting as a temperature control means, performs feedback control to the Peltier element 31 based on the temperature measurement result, thereby maintaining each temperature control block 32 at a predetermined temperature. In this embodiment, thermocouples are used as the temperature measuring means 34 in the heating station S1 and the temperature increasing station S3, whereas a platinum temperature sensor is used as the temperature measuring means 34 in the annealing station S2. These thermocouples and platinum temperature measuring elements are provided so as to be in contact with the temperature adjustment block 32 while being inserted into the inspection table 5 . The platinum temperature detector provided in the annealing station S2 is capable of more precise temperature measurement than the thermocouple, which allows for more precise temperature control by the Peltier element 31. In other words, in the annealing station S2, by providing a temperature control means 7 in a one-to-one relationship to correspond to each storage section 11 of the test container 2, it is possible to individually control the temperature of all storage sections 11, and further by using a platinum thermometer as the temperature measurement means 34, precise temperature control is possible, and the annealing temperature can be accurately adjusted to a temperature that depends on the primers, which are important for hybridization.

[0027] As shown in Figure 2, in the inspection station S4, three through holes 5b are provided on a circumference common to each of the temperature control stations S1 to S3 along the movement path of the inspection container 2 on the inspection table 5, and the storage sections 11 aligned in an arc shape on the inspection container 2 pass above these three through holes 5b. Each through hole 5b is provided with a fluorescence detection means 8 as shown in Figure 6, and the fluorescence detection means 8 includes a light-emitting element 35 provided below each through hole 5b and irradiating excitation light horizontally, a dichroic mirror 36 that reflects the irradiated excitation light upward and passes through the through hole 5b, and a light-receiving element 37 that receives, through the dichroic mirror 36, the fluorescence emitted from the test liquid contained in the storage section 11 of the test container 2 when irradiated with the excitation light. As described above, the inspection container 2 passes through the inspection station S4 without stopping, and at the inspection station S4, the rotating support 21 is positioned at a distance by the cam 21f, so that the inspection container 2 moves without coming into contact with the inspection table 5. As the storage section 11 passes through the three through holes 5b sequentially, the test container 2 receives the excitation light irradiated by the light-emitting element 35 in the test area 11a of the storage section 11, and when the amplification product contained in the test liquid reacts with the excitation light and emits fluorescence according to the wavelength of the excitation light, the fluorescence passes through the dichroic mirror 36 and is received by the light-receiving element 37. In this embodiment, all the containers 11 of the cuvettes 2 passing through the inspection station S4 are irradiated with excitation light and receive fluorescent light every time the cuvettes 2 pass through.

[0028] The light emitting element 35 and the light receiving element 37 constituting each of the fluorescence detecting means 8 provided corresponding to the three through holes 5b are provided with an optical filter 35a and an optical filter 37a that transmit fluorescence of a different single wavelength, respectively. As a result, the light-emitting element 35 irradiates excitation light of different wavelengths from each of the three through holes 5b to one of the storage sections 11 of the test container 2 passing above the three through holes 5b, and the light-receiving element 37 receives visible light of a longer wavelength than the excitation light that is emitted in response to the excitation light of each wavelength. Specifically, in this embodiment, a reaction solution containing Cy5 as a fluorescent dye for detecting influenza A, ROX as a fluorescent dye for detecting influenza B, and FAM as a fluorescent dye for detecting coronavirus (SARS-CoV-2) is used. The control means 9 determines whether or not there is a fluorescent reaction based on the reception of visible light by each light receiving element 37, and determines which virus is present based on which of the three light receiving elements 37 receives light. In this way, the presence or absence of the target virus is determined based on the presence or absence of light received by each light receiving element 37. With this configuration, the PCR testing device 1 of this embodiment enables multiplex PCR testing that can detect multiple viruses.

[0029] The operation of the PCR testing device 1 having the above configuration will be described. First, a medical professional prepares a test liquid by mixing a specimen such as a nasopharyngeal swab, sputum, or saliva collected from a patient with a required reaction liquid, and then uses a micropipette to inject the test liquid into the injection port 16 on the surface of the test container 2. Note that in this embodiment, it is possible to simultaneously test eight people at a time, but it is not necessary to inject the test liquid into all of the containers 11. After the test liquid is thus poured into each container 11 of the cuvette 2, a cover film 14 is attached to the top surface of the main body 12 as shown in FIG. 5, and the inlet 16 and outlet 17 are closed. Next, a medical professional turns on the power, opens the lid portion 4, and sets the test container 2 in the PCR testing device 1. When the power is turned on, the CPU constituting the control means 9 starts up and preheats each of the temperature adjustment stations S1 to S3. When setting the test container 2, the medical professional engages the engagement hole 15a of the support piece 15 of the test container 2 with the support pin 21d formed on the rotating support 21, thereby supporting the end of the test container 2 on the rotating support 21. In addition, when the lid portion 4 is opened, the stopping position is controlled by the control means 9 so that the cutout portion 21g for supporting the test container 2 in the rotating support 21 is always positioned on the front side of the PCR testing device 1 where the touch panel 3a is located. In this embodiment, the inspection station S4 is located on the front side, the heating station S1 is located on the right side, the heating station S3 is located on the left side, and the annealing station S2 is located on the rear side, and when the inspection is completed, the inspection container 2 is positioned at the inspection station S4 and the rotating support 21 is stopped. After the test container 2 is supported on the rotating support 21, the medical staff closes the lid portion 4, causing the inner lid 22 to abut against the test container 2 supported on the rotating support 21 from above and the abutment portion 21e of the annular flat plate portion 21b, thereby biasing them from above.

[0030] When the cover 4 is closed, the control means 9 first operates the driving means 23 of the moving means 6 to rotate the rotary support 21 clockwise several times, and irradiates the cuvette 2 with excitation light at the inspection station S4. As a result, by using any of the three fluorescence detection means 8, excitation light is sequentially irradiated from the light-emitting element 35 to the storage sections 11 passing over the through hole 5b, and the difference in the received light intensity detected by the light-receiving element 37 is used to distinguish between storage sections 11 containing the test liquid and empty storage sections 11. In addition, the control means 9 recognizes the position of each of the storage sections 11 of the test container 2 in the rotation direction based on the rotation angle of the marker of the rib 21c detected by the origin detection means 25, and stores each storage section 11 in association with the detection result of the fluorescence detection means 8 as to whether or not the test liquid is stored. In this case, for example, the storage section 11 at the head of the test container 2 moving clockwise is numbered as number 1, and the storage sections 11 up to number 8 are individually identified. In this way, the control means 9 is able to recognize which storage section 11 contains the test liquid, and selects and operates the temperature adjustment means 7 corresponding to the storage section 11 containing the test liquid to perform temperature adjustment for PCR. The light emitting element 35 and light receiving element 37 of the fluorescence detection means 8 and the control means 9 operated in this way constitute a detection means for detecting whether or not the test liquid is stored. When the rotating support 21 rotates, the rotating support 21 moves up and down between the separated position and the contact position depending on the amount of protrusion of the cam 21f that approaches the cam follower 26, and when the supported inspection container 2 approaches each of the temperature control stations S1 to S3, it descends to the contact position, and when it leaves each of the temperature control stations S1 to S3, it rises to the isolated position, and passes through the inspection station S4 without descending and remaining in the isolated position. In addition, the determination of whether or not each storage section 11 contains the test liquid is not limited to being done by the above-mentioned detection means. Prior to the test, the operator may check the test container 2 and select the number of the storage section 11 containing the test liquid on the touch panel 3a as an input means, and the control means 9 may select and operate the temperature adjustment means 7 corresponding to the storage section 11 with the input number.

[0031] Here, in order to amplify the nucleic acid molecules contained in the test liquid contained in the test container 2, the nucleic acid molecules must be subjected to reactions in the order of thermal denaturation, hybridization, and extension reaction, and this cycle must be repeated several dozen times. In order to cause each of the above reactions to occur, it is necessary to raise the temperature of the test liquid to a temperature appropriate for each reaction. In this embodiment, a preheating operation is performed to preheat the test liquid before causing each of the above reactions to occur. For this preheating operation, the control means 9 positions the inspection vessel 2 on the temperature-raising station S3. At this time, the rotary support 21 is lowered to the contact position by the cam 21f of the axial movement means 24, so that the inspection vessel 2 comes into contact with the surface of each temperature adjustment block 32 of the temperature-raising station S3. At this time, since the inner lid 22 provided on the lid portion 4 urges the rotation support 21 toward the inspection table 5 by the urging force of the spring 27 , the inspection container 2 is pressed against the temperature adjustment block 32 . 2, the temperature-raising station S3 is provided with four temperature control blocks 32 constituting the temperature control means 7, and one temperature control block 32 preheats two adjacent storage sections 11 of the testing container 2. In this case, the temperature control means 7 that do not store the test liquid in the corresponding two storage sections 11 are not operated, and the other temperature control means 7 are selectively operated. During preheating, the temperature adjustment means 7 of the temperature-raising station S3 maintains the temperature control block 32 at a preheating temperature, for example 42°C, which is lower than the temperature control temperatures of any of the temperature control stations S1 to S3, and heats the test liquid in the storage section 11 by contacting the temperature control block 32 with the test container 2 for a predetermined time, for example 180 seconds, until the preheating temperature is reached.

[0032] Next, the control means 9 positions the cuvette 2 at the heating station S1. At this time, the cuvette 2 passes through the inspection station S4. During the movement, the rotary support 21 is elevated to the separated position by the cam 21f of the axial movement means 24, so that the cuvette 2 moves without contacting the bottom surface of the inspection table 5. When the test container 2 stops at the heating station S1, the rotating support 21 is lowered to the contact position by the cam 21f, and the inner lid 22, biased by the spring 27, presses the test container 2 against each temperature control block 32 of the temperature adjustment means 7. As shown in FIG. 2, the heating station S1 is provided with four temperature adjustment blocks 32, and each temperature adjustment block 32 is adapted to have two adjacent storage sections 11 positioned therein. In the temperature adjustment means 7 of the heating station S1, the temperature adjustment block 32 is maintained at a predetermined thermal denaturation temperature, for example, 95° C., and the test container 2 is brought into contact with the temperature adjustment block 32 for a predetermined time for thermal denaturation, for example, 3 seconds, to heat the test liquid in the storage section 11 and cause thermal denaturation of the nucleic acid molecules contained in the test liquid. In this case, too, the temperature adjustment means 7 for which the test liquid is not stored in the two corresponding storage sections 11 is not operated, and the other temperature adjustment means 7 are selectively operated.

[0033] Next, in the annealing process in the annealing station S2, which is the process following the heating process in the heating station S1, the test liquid must be subjected to an annealing temperature that is lower than the temperature required for thermal denaturation, for example, 60°C, as described below, and therefore the temperature of the heated test liquid must be reduced. Therefore, in this embodiment, in the temperature adjustment means 7 of the heating station S1, the control means 9 heats the test container 2 at 95°C for 3 seconds, and then, while keeping the test container 2 pressed against the heating block 32, switches the current direction of the Peltier element 31 to cause the temperature control block 32 to dissipate heat, thereby lowering the temperature of the temperature control block 32 from the thermal denaturation temperature to a temperature lower than the annealing temperature, for example 50°C, and sets up a cooling process in which the test liquid is cooled to a temperature lower than the annealing temperature. As another cooling operation method, after heating the inspection container 2 in the heating station S1, the rotating support 21 can be rotated in the reverse direction, i.e. counterclockwise, by the moving means 6, and stopped on the inspection station S4 where the temperature control means 7 is not provided, and left at the inspection station S4 for a predetermined time to allow natural cooling. After a predetermined time has elapsed, the rotating support 21 continues to rotate in the reverse direction, and the cuvette 2 is moved counterclockwise through the heating station S3 to the annealing station S2. In this case, in order to actively cool the inspection container 2 at the inspection station S4, a cooling material may be placed on the surface of the inspection table 5 below the stopping position of the inspection container 2, or cooling gas may be blown out from the through hole 5b.

[0034] When the thermal denaturation step and the cooling step are thus completed, the control means 9 operates the moving means 6 to position the test container 2 at the annealing station S2, and transition to the hybridization step is made. The rotating support 21 supporting the test vessel 2 descends to the contact position when stopped by the cam 21f, and the test vessel 2 is pressed against the surface of each temperature control block 32 of the temperature adjustment means 7 by the inner lid 22 biased by the spring 27. As shown in FIG. 2, the annealing station S2 is provided with eight temperature adjustment blocks 32, and one accommodation unit 11 is located corresponding to each temperature adjustment block 32. In the temperature adjustment means 7 of the annealing station S2, the temperature adjustment block 32 is maintained at a predetermined annealing temperature, for example, 60° C., and the test container 2 is brought into contact with the temperature adjustment block 32 for a predetermined time for hybridization to occur, for example, 5 seconds, thereby causing hybridization in the nucleic acid molecules contained in the test liquid. In this case, too, the temperature adjustment means 7 whose corresponding storage section 11 does not contain the test liquid is not operated, and the other temperature adjustment means 7 are selectively operated.

[0035] When the annealing step is thus completed, the control means 9 subsequently operates the moving means 6 to move the cuvette 2 clockwise to position it at the temperature-raising station S3 and proceed to the extension reaction step. The rotating support 21 supporting the test vessel 2 descends to the contact position when stopped by the cam 21f of the axial movement means 24, and the test vessel 2 is pressed against the surface of each temperature control block 32 of the temperature adjustment means 7 by the inner lid 22 biased by a spring 27. In the temperature-raising station S3, four temperature control blocks 32 which constitute a temperature adjustment means 7 are provided, similar to the heating station S1, and when the inspection container 2 stops at the temperature-raising station S3, two storage sections 11 are positioned for each temperature control block 32. Then, in the temperature adjustment means 7 of the temperature-raising station S3, immediately after the completion of the preheating step, the Peltier element 31 heats and maintains the temperature adjustment block 32 at a predetermined extension reaction temperature, for example, 75° C., and the test container 2 is brought into contact with the temperature adjustment block 32 for a predetermined time for an extension reaction to occur, for example, one second, to cause an extension reaction in the nucleic acid molecules contained in the test liquid in the storage section 11. In this case, too, the temperature adjustment means 7 for which the two corresponding storage sections 11 do not contain the test liquid are not operated, and the other temperature adjustment means 7 are selectively operated.

[0036] Then, PCR is carried out, which consists of the above-mentioned thermal denaturation step, annealing step, and extension reaction step, but in order to detect viruses with high accuracy, it is necessary to amplify the nucleic acid molecules sufficiently to obtain a sufficient amount of amplified product, so the above-mentioned thermal denaturation extension PCR cycle is repeated several tens of times, and in this embodiment, this is carried out for 45 cycles. During this time, the test container 2 moves in a rotational direction within the environment closed by the lid portion 4, but the temperature of the PCR testing device 1 itself rises due to heat generated by the driving means 23 of the moving means 6 and radiant heat from the temperature control block 32 of the temperature control means 7, and the environmental temperature of the testing space partitioned by the lid portion 4 and the testing table 5 also rises. Therefore, even if the Peltier element 31 is operated at a constant temperature, the expected temperature control will not be performed, and there is a risk that it will affect each PCR reaction. Therefore, in each of the temperature control stations S1 to S3, the temperature of each temperature control block 32 of the temperature adjustment means 7 is constantly measured by a temperature measuring means 34 provided in each of the temperature adjustment stations, and the control means 9 feedback controls the temperature of each Peltier element 31 based on the measurement results, thereby maintaining each temperature control block 32 at a predetermined temperature. In particular, in the annealing station S2, it is necessary to accurately adjust the annealing temperature to a primer-dependent temperature, which is important for hybridization of the test liquid, and each storage section 11 is provided with a temperature control block 32, a Peltier element 31, and a temperature measurement means 34, and the temperature measurement means 34 measures the temperature of the temperature control block 32 using a platinum thermometer temperature measurement means 34, which has higher detection accuracy than a thermocouple. Furthermore, four temperature control blocks 32 are provided in the heating station S1 and the temperature-raising station S3, and eight are provided in the annealing station S3, and the temperature of the temperature control blocks 32 is controlled corresponding to each of the eight storage sections 11 of the test container 2.By first identifying the storage section 11 containing the test liquid in the control means 9, the temperature adjustment means 7 is selectively operated to stop heating the Peltier element 31 of the temperature control block 32 corresponding to the empty storage section 11. This makes it possible to suppress the amount of heat generated in each of the temperature adjustment stations S1 to S3, and to suppress increases in the environmental temperature of the PCR testing device 1 itself, the testing space partitioned by the lid part 4 and the testing table 5, and the temperatures of the testing table 5 and the testing container 2. This makes it possible to reduce the time required for the cooling step performed between the heating step and the annealing step described above, and also makes it possible to shorten the testing time throughout the entire cycle. The temperature adjustment means 7 may be selectively operated in all of the temperature adjustment stations S1 to S3 as in this embodiment, but may also be operated in any of the stations.

[0037] In the above-mentioned inspection station S4, excitation light of different wavelengths is constantly irradiated upward from the light-emitting elements 35 of the fluorescence detection means 8 provided corresponding to each of the three through holes 5b, and a light receiving signal is constantly input to the control means 9 from the light-receiving element 37. When the test container 2 moves from the temperature-raising station S3 to the heating station S1, and passes above each through hole 5b of the test station S4, the light-receiving element 37 receives the fluorescence emitted from the test liquid when excitation light is irradiated onto the test container 2, and the control means 9 records the test results based on the fluorescence detection for each storage section 11 of the test container 2. Based on the obtained test results, the control means 9 determines whether the test liquid contained in each storage section 11 in the test container 2 is infected with a virus and identifies the type of virus that is infected, and displays the test results on the touch panel 3a on the front side of the housing 3. Incidentally, since a correct determination cannot be made while the number of amplification cycles is small, fluorescence detection may be performed after a predetermined number of cycles have been completed.

[0038] Here, when using the PCR testing device 1 for the first time or after each specified number of PCR tests, operation can be checked to see whether the virus can be correctly detected using negative and positive mock test liquids. The negative and positive mock test liquids are placed in the designated storage section 11 of the test container 1, and the test container 1 is set on the rotating support 21 of the PCR testing device 1. In this state, the touch panel 3a is used to instruct the control means 9 to perform an operation check. Then, the control means 9 rotates the rotary support 21 to pass the cuvette 1 above the inspection station S4, and causes each fluorescence detecting means 8 to irradiate it with excitation light. As a result, the photodetector 37 does not receive any fluorescence in the case of a negative pseudo test liquid, but receives a specified fluorescence in the case of a positive pseudo test liquid, thereby making it possible to confirm that normal virus detection is being performed and that the PCR testing device 1 is operating properly. The negative and positive pseudo test liquids may be stored together with the test liquid in the test container 2. In this case, the PCR test will be performed directly after the above-mentioned operation check, but the number of storage parts 11 that can store the test liquid in the test container 2 will be reduced.

[0039] Thus, according to the PCR testing device 1 of this embodiment, the test liquid is stored in a testing container 2 equipped with multiple storage sections 11, and PCR is performed by repeatedly moving this in sequence to each of the temperature control stations S1 to S3.Since it is possible to adjust the temperature of the test liquid corresponding to each storage section 11, PCR can be performed reliably in each storage section 11, making it possible to make an accurate determination. At this time, the moving means 6 rotates the rotating support 21 by the rotating shaft 23a of the driving means 23 fixed to the inspection table 5, and this rotating support 21 is moved in the axial direction relative to the rotating shaft 23a by the axial moving means 24. By moving the rotating support 21 relative to the driving means 23 in this manner, tilting of the rotation axis 23a is less likely to occur compared to when the rotating support 21 is moved axially together with the driving means 23, and the rotating support 23 can be rotated with high precision. For example, in the annealing station S2, it is possible to properly contact the eight storage sections 11 of the inspection container 2 with the eight temperature control blocks 32 that constitute the temperature adjustment means 7 without any misalignment or tilt. In the above embodiment, the temperature control means 7 of the annealing station S2 is configured to include the same number of Peltier elements 31, temperature control blocks 32, and temperature measurement means 34 as the number of the storage sections 11 of the test containers 2, but this may also be deployed in the heating station S1 or the temperature increasing station S3. [Explanation of symbols]

[0040] 1 PCR testing device (testing device) 2 Test container 5 Examination table 6 Transportation 7 Temperature control means 8 Fluorescence detection means 9 Control means (temperature control means) 11 Storage section 21 Rotating support 21a Boss 21f Cam 22 Inner lid 23 Driving means 23a Rotating shaft 24 Axial movement means 31 Peltier element (thermoelectric element) 32 Temperature control block 34 Temperature measuring means S1 Heating station S2 Annealing station S3 Heating station S4 Inspection station

Claims

1. In a testing device in which a test container having a container portion for containing a test liquid is moved in sequence to contact a plurality of temperature control units arranged on a common circumference, a rotating shaft that rotates at the center of a circumference on which the plurality of temperature control units are arranged, a rotating support that is rotated by the rotating shaft to support the cuvette and move it to the plurality of temperature control units, and an axial movement means that moves the rotating support in the axial direction relative to the rotating shaft, The rotating support supports an end of the test vessel so that the bottom of the test vessel is in contact with the temperature control unit, An inspection device characterized in that, when positioning the inspection vessel in the temperature control section, the axial movement means positions the rotating support at a contact position where the inspection vessel contacts the temperature control section, and, when moving the inspection vessel from the temperature control section, the axial movement means positions the rotating support at a separated position where the inspection vessel is separated from the temperature control section.

2. a biasing means for biasing the cuvette against the rotary support and biasing the rotary support in a direction from the separated position toward the contact position; The inspection device described in claim 1, characterized in that when the rotating support is positioned at the contact position by the axial moving means, the inspection container is pressed against the temperature control unit while being biased against the rotating support by the biasing means, and when the inspection container is moved from the temperature control unit, the axial moving means positions the rotating support at the separated position against the biasing force of the biasing means while the inspection container is biased against the rotating support.

3. The rotating support is formed in a substantially disk shape, and supports the cuvette in a notch formed in an outer periphery thereof, The inspection device described in claim 1 or claim 2, characterized in that the axial movement means includes a ring-shaped cam provided on the rotating support surrounding the rotating shaft, and the rotating support is moved between the contact position and the separation position by the action of the cam accompanying the rotation of the rotating support.

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