The present disclosure relates to an analytical device.
In the field of point of care testing (POCT), a known analytical device performs analysis of a test substance sample, such as measurement of the concentration of a specimen included in the test substance sample. There is a device that performs, as an example of analysis of a test substance sample, measurement of the concentration of a specimen included in a test substance such as blood or urine. For example, WO2013/161664A discloses an analytical device that detects a color reaction by using a dry analysis chip including a spreading layer in which a test substance sample is to be spread and a reaction layer having a reagent.
When such an analysis chip is used, a test substance sample spreads in the spreading layer upon being spotted onto the spreading layer of the analysis chip. When the test substance sample reaches the reaction layer, a specimen in the test substance sample reacts with the reagent in the reaction layer and produces a reaction substance that develops color. The analytical device described in WO2013/161664A can measure the concentration of a specimen in a test substance sample by irradiating the reaction layer, where the test substance sample reacts with the reagent, with detection light that is from a light source and that includes light of a wavelength to be absorbed by a reaction substance that develops color, and acquiring a detection signal corresponding to reflected light from the reaction layer.
The analytical device described in WO2013/161664A includes an incubator and incubates the analysis chip spotted with the test substance sample for a predetermined time in the incubator. A disc-shaped rotary member is included inside the incubator, and multiple element chambers (cells) in which analysis chips are to be arranged are provided on the rotary member. Each element chamber is constituted by a concave section formed on an upper surface of the rotary member and a pressing member disposed above each concave section to face the concave section. Each analysis chip is inserted into the element chamber and held in a state of being pressed against the concave section by the pressing member.
In the analytical device, as exemplified in WO2013/161664A, using dry analytical chips, multiple analysis chips corresponding to multiple measurement items are included to allow specification and testing of desired test items. As mentioned earlier, the specimen in the test substance sample reacts with the reagent in the reaction layer of the analysis chip and produces a reaction substance that develops color. Even after the analysis chip is discharged, this reaction substance may remain in the cell. Therefore, an analysis chip to be analyzed next may be loaded into a cell while a reaction substance produced at a previous analysis chip still remains in the cell. Depending on the measurement item for the next analysis chip, there are a case where analysis can be performed without any problem and a case where an event called carryover, in which a measured value is increased due to an influence of a reaction substance remaining in a cell, occurs. When carryover occurs, the reliability of the analysis results is significantly reduced.
The technology according to the present disclosure provides an analytical device that can suppress measurement errors due to carryover and perform measurement with higher reliability than the related art when analyzing a test substance sample by using a dry analysis chip.
The analytical device according to the present disclosure is an analytical device on which a plurality of analysis chips are to be detachably loaded, the plurality of analysis chips each having a reaction region in which a reagent for a corresponding measurement item is immobilized and each being provided, outside the reaction region, with item information related to the corresponding measurement item, the analytical device being configured to analyze a plurality of measurement items for a test substance sample by spotting the test substance sample onto the reaction region of each of the plurality of analysis chips and measuring a state of a reaction between the test substance sample and the reagent, the analytical device including:
The memory may store combination information related to a target combination that is a combination of a plurality of pieces of the item information with a possibility of occurrence of carryover. It may be configured such that, in the carryover suppression processing, the processor executes, based on the combination information, combination determination processing of determining whether a combination of the previous item information acquired from the stain-related information on the to-be-used cell and the current item information of the to-be-loaded analysis chip acquired through the item-information reading unit corresponds to the target combination and executes preset processing when determined that the combination corresponds to the target combination in the combination determination processing.
The processor may be configured to, as the preset processing, determine presence or absence of the stain on the to-be-used cell based on the stain information acquired from the stain-related information on the to-be-used cell and change the to-be-used cell when determined that the stain is present.
The processor may be configured to, as the preset processing, determine presence or absence of the stain on the to-be-used cell based on the stain information acquired from the stain-related information on the to-be-used cell and stop measurement using the to-be-used cell when determined that the stain is present and execute processing related to cleansing of the pressing member for the to-be-used cell.
The analytical device may further include a cleansing mechanism that cleans the pressing member, and the processor may be configured to cause the cleansing mechanism to cleanse, as the processing related to the cleansing, the pressing member for the to-be-used cell.
The processor may be configured to issue a warning, as the processing related to the cleansing, to prompt a user to cleanse the to-be-used cell.
The processor may be configured to execute, after the stain-related information is acquired, processing related to cleansing of the pressing member for the cell determined to have the stain based on the stain information, regardless of whether subsequent measurement is to be started.
The target combination may include two combinations that are a combination of a measurement item to be measured first and producing a reaction substance affecting pH and a measurement item to be measured later and for which a pH indicator is used as the reagent and a combination of a measurement item to be measured first and producing ammonia as a result of a reaction between a specimen in the test substance sample and the reagent and a measurement item to be measured later and for which ammonia is measured.
In the stain detection mechanism, a detection unit used in measurement of a state of a reaction between the test substance sample and the reagent may also serve as the detection unit that detects the stain on the pressing member.
With the technology according to the present disclosure, when analyzing a test substance sample by using a dry analysis chip, it is possible to suppress the occurrence of measurement errors due to carryover and possible to perform measurement with higher reliability than the related art.
Hereinafter, preferred embodiments of the present invention will be described with reference to the drawings.
The analytical device 100 according to one embodiment of the present disclosure illustrated in
The analytical device 100 includes a chip set section 10, a reader 20, a test-substance spotting section 30, a chip transport mechanism 40, a test-substance spotting mechanism 50, an incubator 60, a detection unit 70, a chip disposal mechanism 80, a processor 90, and a memory 92.
In the chip set section 10, a stocker 14 for storing analysis chips 12 is disposed on a holding base 11. Multiple analysis chips 12 are stacked and stored in the stocker 14.
As illustrated in
Each analysis chip 12 has a carrier 16 onto which a test substance sample is spotted, and the carrier 16 is accommodated in a case 17. The case 17 is constituted by a first case 17A and a second case 17B and accommodates the carrier 16 such that the carrier 16 is sandwiched between the first case 17A and the second case 17B. An opening 17C that functions as a dropping port for spotting a test substance sample onto the reaction region 12A is formed in the first case 17A. An opening 17D for irradiation of the reaction region 12A with light is formed in the second case 17B. The carrier 16 is exposed through the opening 17C of the first case 17A constituting the front surface of the analysis chip 12. The carrier 16 is exposed through the opening 17D of the second case 17B constituting the back surface of the analysis chip 12. A region of the carrier 16 exposed through the opening 17D constitutes the reaction region 12A where the reagent is immobilized. The second case 17B is provided with an information code 17E in which item information related to a measurement item is encoded. The information code 17E is, for example, a pattern in which multiple dots are arranged, and the arrangement pattern of the dots is different for each measurement item. Naturally, as the information code 17E, a one-dimensional barcode, a two-dimensional barcode, or the like may be used.
By changing the reagent to be reacted with a test substance sample, it is possible to analyze multiple measurement items for the test substance sample. Multiple analysis chips 12 are prepared for respective measurement items, and a reagent corresponding to a measurement item is immobilized at the carrier 16 of each of the analysis chips 12. Item information provided for each analysis chip 12 is, for example, identification information (such as reagent name and identification code) on a reagent immobilized at the carrier 16 of the analysis chip 12 or identification information (such as item name and identification code) on a measurement item to be measured with the reagent.
In
The reader 20 is constituted by, for example, an image sensor such as a charge coupled device (CCD) or a complementary metal oxide semiconductor (CMOS). The item information read by the reader 20 is output to the processor 90.
In the test-substance spotting section 30, a test substance such as blood plasma, whole blood, serum, or urine is spotted onto each analysis chip 12. The test-substance spotting section 30 is provided with a chip support base 31, and spotting of the test substance sample onto each analysis chip 12 transported onto the chip support base 31 is performed on the chip support base 31. The test substance sample is spotted by the test-substance spotting mechanism 50 described later. The chip support base 31 is disposed adjacent to the holding base 11.
As illustrated in
As illustrated in
In
In
The incubator 60 has a substrate 62 provided with multiple cells S1 to S13 in each of which a corresponding one of the analysis chips 12 is to be loaded. In the present example, the substrate 62 is annular in shape, and thirteen cells S1 to S13 are arranged along the circumference. In the following description, when it is necessary to distinguish the multiple cells S1 to S13 from each other, the multiple cells S1 to S13 will be denoted with sub-reference numerals 1 to 13, and when distinction thereof is not necessary, the multiple cells S1 to S13 will simply be referred to as the cell S. The cell S is, for example, a concave section having a size and a shape with which the cell S can accommodate the analysis chip 12. The cell S is an example of a loading portion on each of which the analysis chip 12 is to be loaded.
As illustrated in
A rotary cylinder 66 is provided at a lower surface of the substrate 62. The rotary cylinder 66 has a substantially inverted triangular cross-sectional shape in which the inner diameter decreases toward the lower side. A bearing 67 is disposed at a lower portion of the outer periphery of the rotary cylinder 66, and the rotary cylinder 66 is rotatably supported by the bearing 67. The holding member 65 rotates integrally with the substrate 62. A bottom portion of the rotary cylinder 66 forming the vertex of the inverted triangle is open, and this opening functions as a disposal hole 68 for discarding of used analysis chips 12. Each used analysis chip 12 is moved in a state of being loaded in the cell S toward the center side of the annular substrate 62 and is dropped toward the inclined surface of the rotary cylinder 66. Each used analysis chip 12 dropped into the rotary cylinder 66 slides on the inclined surface and is discarded through the disposal hole 68.
The holding member 65 is provided with heating means (not illustrated), and the analysis chips 12 in the cells S1 to S13 are maintained at a constant predetermined temperature by the temperature adjustment of the heating means. A thermal cover 69 is installed on the upper surface of the holding member 65. In
An aperture window 62A for photometry is formed at the center of the bottom surface of each of the cells S1 to S13 on the substrate 62, and the reflectance optical density of each of the analysis chips 12 is measured through the aperture windows 62A by the detection unit 70 disposed at the position illustrated in
As illustrated in
The light source 72 irradiates the reaction region 12A with light through the opening 17D of the case 17 of the analysis chip 12. The wavelength range of the light is determined according to a specimen (that is, a measurement item). For example, as mentioned above, a reaction substance that develops a specific color is generated by a reaction between a specimen and a reagent in the present example. Since the light with which the light source 72 performs irradiation is detection light for detecting whether a reaction substance has been generated, the wavelength range is determined according to a color developed by the reaction substance. The detection light in this example is, for example, light that includes a wavelength range absorbed by a reaction substance in order to detect the reaction substance.
In particular, it is preferable that the wavelength range of the detection light L0 is limited to the wavelength range absorbed by the reaction substance. As the light source 72, a light source such as a light emitting diode (LED), an organic electro luminescence (EL), or a semiconductor laser is used, for example. Detection light limited to a specific wavelength range may be generated by a combination of a light source that emits light in a relatively broad wavelength range, such as a white light source, and a bandpass filter that transmits only the specific wavelength range. Although only one light source 72 is illustrated in
The photodetector 74 detects output light L1 output from each analysis chip 12 when the analysis chip 12 is irradiated with the detection light L0. The photodetector 74 is, for example, a light-receiving element such as a photodiode that outputs a detection signal corresponding to the amount of light. In this example, two photodetectors 74 are included. The photodetector 74 outputs a detection signal to the processor 90. The processor 90 acquires a detection signal corresponding to the output light L1 and derives the concentration of a specimen.
In the reaction region 12A, the test substance sample reacts with the reagent and produces a reaction substance that develops a specific color. Due to the generation of the reaction substance, the color of the reaction region 12A changes, and this color change appears as a change in the optical density of the reaction region 12A. The output light L1 corresponds to the optical density of the reaction region 12A and reflects information about the reaction substance due to light absorption by the reaction substance, and the like. The optical density of the reaction region 12A changes according to the amount of the reaction substance, and the amount of the reaction substance represents the concentration of the specimen in the test substance sample. Therefore, the concentration of the specimen can be measured on the basis of the detection signal representing output light including information about the reaction substance.
The reaction substance generated when the test substance sample reacts with the reagent may adhere to a pressing surface 64A of the pressing member 64. Since the reaction substance is generated by the reaction between the test substance sample and the reagent in the analysis chip 12, a stain due to the adhesion of the reaction substance to the pressing member 64 is a stain caused by the loaded analysis chip that is the analysis chip 12 loaded in the cell S in previous measurement. The detection unit 70 also functions as a stain detection mechanism that detects a stain adhering to the pressing surface 64A of the pressing member 64.
The reflected light L2 detected by the photodetector 74 includes information on whether a stain has adhered to the pressing member 64. The photodetector 74 outputs a stain detection signal corresponding to the reflected light L2 to the processor 90. The processor 90 determines whether a stain has adhered to the pressing member 64 on the basis of the stain detection signal corresponding to the reflected light L2. Then, the processor 90 records in the memory 92 that the detected cell S is stained when determined that a stain is present on the pressing member 64 and records in the memory 92 that the detected cell S is not stained when determined that no stain is present on the pressing member 64. The detection unit 70 and the processor 90 constitute a stain detection mechanism.
The chip disposal mechanism 80 is attached to the incubator 60. The chip disposal mechanism 80 pushes out and drops the used analysis chip 12 after measurement to a center portion of the incubator 60 and discards the analysis chip 12.
The chip disposal mechanism 80 includes a disposal bar 82 that moves back and forth in a slit-shaped space above the cell S in a direction from the outer peripheral side toward the center. A collection box for collecting used analysis chips 12 is disposed below the disposal hole 68.
The processor 90 has, for example, a CPU and a memory and executes processing in the analytical device 100 by the CPU executing a program. The processor 90 also comprehensively controls each part of the analytical device 100.
The memory 92 stores, for example, a test program. Additionally, the memory 92 stores stain-related information related to the cells S1 to S13. For example, as illustrated in
When the processor 90 receives an instruction to start a test of the analysis chip 12, the processor 90 acquires, before a to-be-loaded analysis chip (hereinafter referred to as the to-be-loaded analysis chip 12n) is loaded into a to-be-used cell (hereinafter referred to as the to-be-used cell Sn) that is the cell S to be used in current measurement, stain-related information stored in the memory 92 and related to the to-be-used cell Sn. The processor 90 also acquires a measurement item for the to-be-loaded analysis chip 12n from the reader 20. Then, on the basis of the stain-related information and current item information that is the item information of the to-be-loaded analysis chip 12n, the processor 90 executes carryover suppression processing for suppressing carryover, in which a stain due to previous measurement affects current measurement.
In the carryover suppression processing, the processor 90 executes, for example, combination determination processing of determining, on the basis of the combination information, whether a combination of previous item information acquired from stain-related information on the to-be-used cell Sn and current item information on the to-be-loaded analysis chip 12n acquired through the reader 20 corresponds to a target combination. In other words, it is determined whether the combination of the previous item information and the current item information corresponds to any of the target combinations of the measurement item 1 and the measurement item 2, stored in the memory 92. Then, when determined that the combination corresponds to any of the target combinations, the processor 90 executes preset processing.
As the preset processing, for example, the processor 90 determines the presence or absence of a stain on the to-be-used cell Sn on the basis of the stain information acquired from the stain-related information on the to-be-used cell Sn and changes the to-be-used cell Sn when determined that a stain is present.
An example of the flow of a test including the carryover suppression processing using the analytical device 100 will be described with reference to
As illustrated in
Next, for the to-be-used cell Sn where the to-be-loaded analysis chip 12n is to be measured, the processor 90 reads out a measurement item in previous measurement performed in the to-be-used cell Sn from the memory 92. The processor 90 then determines whether a combination of the previous measurement item and the current measurement item corresponds to a target combination with a possibility of occurrence of carryover. The processor 90 determines whether the combination of the previous measurement item and the current measurement item corresponds to any of the target combinations of the measurement item 1 and the measurement item 2 shown in
When determined that the combination of the previous measurement item and the current measurement item does not correspond to the target combination (step ST12: NO), the processor 90 loads the to-be-loaded analysis chip 12n into the to-be-used cell Sn (step ST13). On the other hand, if it is determined that the combination of the previous measurement item and the current measurement item corresponds to a target combination (step ST12: YES), it is determined whether the to-be-used cell Sn is stained (step ST14). Here, stain information on the pressing surface 64A of the pressing member 64 acquired after the previous measurement and before the current measurement is read out as stain-related information on the to-be-used cell Sn from memory 92.
If the to-be-used cell Sn is not stained (step ST14: NO), the processor 90 loads the analysis chip 12 into the to-be-used cell Sn (step ST13). If the to-be-used cell Sn is stained (step ST14: YES), the processor 90 determines whether a clean cell is available (step ST15).
If a clean cell is available (step ST15: YES), the to-be-loaded analysis chip 12n is loaded into the clean cell (step ST16). If there are multiple clean cells, the to-be-loaded analysis chip 12n may be loaded into any of the clean cells. If no clean cell is available (step ST15: NO), the to-be-loaded analysis chip 12n is not loaded into a cell and is put on standby (step ST17). The to-be-loaded analysis chip 12n is on standby until a clean cell becomes available and, when a clean cell becomes available, is loaded into the clean cell (step ST16).
Subsequently, the substrate 62 is rotated to move the to-be-loaded analysis chip 12n to the position of the detection unit 70, and photometry is performed with respect to the reaction region 12A of the to-be-loaded analysis chip 12n by the detection unit 70 to detect optical density. The processor 90 acquires a detection signal indicating the optical density from the detection unit 70 (step ST18). The processor 90 derives the concentration of the specimen included in the test substance sample on the basis of the detection signal and outputs a result to a display device (not illustrated) or the like.
The processor 90 records, as a piece of the stain-related information, the No. of the used cell and measured measurement item in the memory 92, that is, stores the stain-related information in the memory 92 (step ST19).
A test of the to-be-loaded analysis chip 12n is performed through the above-described steps.
When the analysis chips 12 are loaded into the incubator 60, in practice, the analysis chips 12 are loaded into one or a plurality of the cells S1 to S13 sequentially, and, after incubation is performed with respect to a plurality of the analysis chips 12, photometry is sequentially carried out for each analysis chip 12.
After measurement of the plurality of the analysis chips 12 loaded together is completed and the analysis chips in all of the cells S1 to S13 are discarded, the processor 90 executes stain detection processing for the pressing surface 64A of the pressing member 64 of each of the cells S1 to S13.
Each of the cells S1 to S13 is subjected at the detection unit 70 to the stain detection processing.
As described above, the analytical device 100 includes the stain detection mechanism and the processor 90. The processor 90 executes the carryover suppression processing for suppressing carryover, in which a stain due to previous measurement affects current measurement, on the basis of the stain-related information and the current item information, which is the item information of a to-be-loaded analysis chip. Therefore, it is possible to reduce errors in measurement values due to carryover. Since it is not necessary to separate cells for each measurement item in advance, the impact on takt time can be minimized. It is possible to reduce the number of analysis chips treated as analysis errors due to measurement performed while carryover occurs and to eliminate waste of test substances. Since the analytical device specifies and sets the order of measurement items automatically, users do not need to perform specification, setting, and the like of the order of measurement items. It is thus possible to reduce burden of users.
In the above embodiment, the memory 92 stores combination information related to target combinations, which are combinations of multiple pieces of item information with a possibility of occurrence of carryover. In the carryover suppression processing, the processor 90 executes, on the basis of the combination information that is information stored in the memory 92, combination determination processing of determining whether a combination of previous item information acquired from stain-related information on a to-be-used cell and current item information of the to-be-loaded analysis chip 12n acquired through the reader 20 corresponds to a target combination. If determined that the combination corresponds to the target combination, the processor 90 executes preset processing. The preset processing is processing for suppressing loading of analysis chips for combinations that cause carryover into cells and can suppress occurrence of measurement errors due to carryover.
In particular, as the preset processing, in the above-described embodiment, the presence or absence of a stain on the to-be-used cell Sn is determined on the basis of the stain information acquired from the stain-related information on the to-be-used cell Sn. If it is determined that a stain is present, the to-be-used cell Sn is changed. This reliably prevents the loading of analysis chips for combinations that cause carryover into cells.
In the above-described embodiment, when stain detection is performed for the pressing surface 64A of the pressing member 64, the presence or absence of a stain is recorded in the memory 92. In addition, the processor 90 may stop measurement using the to-be-used cell Sn when determined that a stain is present and may execute processing related to cleansing of the pressing member 64 for the to-be-used cell Sn. Here, the “cleansing” means removing a stain, and the method of cleansing is not limited. Cleansing includes cleaning by wiping.
For example, the analytical device 100 may include a cleansing mechanism that cleans the pressing member 64 and may cause the cleansing mechanism to clean, as processing related to cleansing, the pressing member 64 for the to-be-used cell Sn.
As the cleansing mechanism, for example, the chip disposal mechanism 80 can be used. As illustrated in
As illustrated in
As described above, by configuring such that presence or absence of a stain on each pressing member 64 is detected and automatic cleaning is performed when a stain is present, it is possible to reduce the number of stained cells and possible to improve measurement efficiency.
In addition to performing automatic cleaning, the processor 90 may perform, as cleansing-related processing, processing of issuing a warning to prompt a user to perform cleansing.
As illustrated in
As described above, as processing related to cleansing of the to-be-used cell, the processor 90 can prompt the user to perform cleaning by issuing a warning prompting the user to perform cleaning. It is possible at least to make the user aware that there is a stain on a cell.
Such processing related to cleansing of the pressing member is preferably executed, regardless of whether subsequent measurement is to be started, for cells determined to be stained on the basis of the stain information after stain-related information is acquired by the stain detection mechanism.
In the analytical device 100 in the above embodiment, the detection unit 70 used for measuring the state of a reaction between a test substance sample and a reagent also serves as a detection unit of the stain detection mechanism that detects a stain on each pressing member 64. A detection unit dedicated to the stain detection mechanism may be included separately from the detection unit 70. However, with the detection unit 70 also serving as the detection unit of the stain detection mechanism, the number of components can be reduced, and the stain detection mechanism can be added to the analytical device 100 at a low cost.
Furthermore, in the above-described embodiment, a processor (processer) of various types mentioned below can be used as the hardware structure of the processor. In addition to a CPU, which is a general-purpose processor functioning as various processing units by executing software (program), the various types of processors includes a programmable logic device (PLD) such as a field-programmable gate array (FPGA) whose circuit configuration can be changed after manufacture and a dedicated electric circuit such as an application specific integrated circuit (ASIC), which is a processor having a circuit configuration specifically designed to execute particular processing.
Moreover, the aforementioned processing may be executed by one of these processors of various types or by a combination of two or more processors of the same or different types (for example, multiple FPGAs or a combination of a CPU and a FPGA, etc.). In addition, multiple processing units may be constituted by a single processor. As an example in which multiple processing units are constituted by a single processor, there is a form that uses a processor that, similarly to a system on chip (SOC), realizes functions of an entire system including multiple processing units by a single integrated circuit (IC) chip.
More specifically, as the hardware structure of these processors, an electric circuit (circuitry) in which circuit elements such as semiconductor elements are combined can be used.
In addition, the technology in the present disclosure is extended not only to an operation program of the analytical device but also to a computer-readable storage medium (USB memory, DVD (digital versatile disc)-ROM (read only memory), etc.) that non-transitorily stores the operation program of the analytical device.
With respect to the above embodiments, the following appendixes are further disclosed.
An analytical device on which a plurality of analysis chips are to be detachably loaded, the plurality of analysis chips each having a reaction region in which a reagent for a corresponding measurement item is immobilized and each being provided, outside the reaction region, with item information related to the corresponding measurement item, the analytical device being configured to analyze a plurality of measurement items for a test substance sample by spotting the test substance sample onto the reaction region of each of the plurality of analysis chips and measuring a state of a reaction between the test substance sample and the reagent, the analytical device including:
The analytical device according to Appendix 1,
The analytical device according to Appendix 2,
The analytical device according to Appendix 2,
The analytical device according to Appendix 4, further including:
The analytical device according to Appendix 4,
The analytical device according to any one of Appendix 1 to Appendix 6,
The analytical device according to any one of Appendix 2 to Appendix 6 and Appendix 7 citing Appendix 2,
The disclosure of JP2022-148391 filed on Sep. 16, 2022 is incorporated herein by reference in its entirety. All publications, patent applications, and technical standards mentioned in this specification are incorporated herein by reference to the same extent as if each individual publication, patent application, or technical standard was specifically and individually indicated to be incorporated by reference.
Number | Date | Country | Kind |
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2022-148391 | Sep 2022 | JP | national |
This application is a continuation of International Application No. PCT/JP2023/021256, filed on Jun. 7, 2023, which claims priority from Japanese Patent Application No. 2022-148391, filed on Sep. 16, 2022. The entire disclosure of each of the above applications is incorporated herein by reference.
Number | Date | Country | |
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Parent | PCT/JP2023/021256 | Jun 2023 | WO |
Child | 19073020 | US |