Cartridge and detection method

A cartridge to be installed in a detection device for detecting light generated from a measurement sample containing a test substance is provided. The cartridge includes: a plurality of detection chambers fluidly isolated from each other and each receiving a measurement sample; and a transmission suppression unit provided between one detection chamber and another detection chamber of the plurality of detection chambers, and configured to suppress transmission of light generated from a measurement sample in the one detection chamber to the another detection chamber.

CROSS REFERENCE TO RELATED APPLICATION

This application claims priority from prior Japanese Patent Application No. 2019-055286, filed on Mar. 22, 2019, entitled “CARTRIDGE AND DETECTION METHOD”, the entire contents of which are incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to a cartridge used for detecting light generated from a measurement sample containing a test substance, and a detection method for detecting a test substance using the cartridge.

BACKGROUND

US Patent Application Publication No. 2003/0054563 discloses a microfluidic device900in which a plurality of detection microcavities903ato903fconnected to a common distribution channel901and a common discharge channel902are formed as shown inFIG.22. Each detection microcavity903a-903fcommunicates on the upstream side with the same common distribution channel901. Each detection microcavity903a-903fhas an outlet to the common discharge channel902. A substance such as a detectable product or reagent is introduced into each of the detection microcavities903ato903f. The radiation of the substance held in each of the detection microcavities903ato903fis detected by a detector external to the microfluidic device900.

US Patent Application Publication No. 2003/0054563 points out a problem of “crosstalk” between the detection microcavities903ato903f. In US Patent Application Publication No. 2003/0054563, therefore, when performing luminescence measurement, a black plastic material that absorbs light and has low autofluorescence is used in the microfluidic device900in a region excluding the detection area (that is, the detection microcavities903ato903f).

SUMMARY OF THE INVENTION

However, in the microfluidic device of US Patent Application Publication No. 2003/0054563, a plurality of detection microcavities in which detection is performed are connected to each other via both a common distribution channel and a common discharge channel. Therefore, a passage connecting a plurality of detection microcavities may act like a light guide for guiding light. That is, there is a possibility that the light generated in one detection microcavity is repeatedly reflected and propagated inside the passage and reaches another detection microcavity.

In this way, in a cartridge including a plurality of detection chambers, when light generated from a measurement sample in one of the detection chambers reaches another detection chamber, extraneous light not derived from the measurement sample in the detection chamber may be mixed therewith, such that the detection accuracy of light generated from the measurement sample decreases. Therefore, in a cartridge including a plurality of detection chambers, it is desirable to suppress light generated in each of the plurality of detection chambers from being mixed into another detection chamber.

The present invention suppresses the light generated in each of the plurality of detection chambers from being mixed into another detection chamber in a cartridge including a plurality of detection chambers.

As shown inFIG.1, the cartridge (100) according to the first aspect of the present invention is installed in a detection device (300) for detecting light generated from a measurement sample (90) containing a test substance, the cartridge (100) including a plurality of detection chambers (10) fluidly isolated from each other and each receiving a measurement sample (90), respectively, and a transmission suppression unit (20) disposed between one detection chamber (10) and another detection chamber (10) of the plurality of detection chambers (10), and configured to suppress transmission of light generated from a measurement sample in the one detection chamber (10) to the other detection chamber (10).

Note that in this specification “fluidly isolated” means that the fluid is not connected via a passage through which the fluid can flow. “Suppress transmission of light generated from a measurement sample in one detection chamber to another detection chamber” means that the amount of transmitted light is less than the amount of incident light when light generated from a measurement sample in one detection chamber and directed to another detection chamber enters the transmission suppression unit, and is not limited to the case where the amount of transmitted light of the light incident on the transmission suppression unit is set to zero. The concept of “suppressing the transmission of light generated from a measurement sample in one detection chamber to another detection chamber” is a concept that allows light other than the light generated from a measurement sample to pass without being suppressed.

In the cartridge (100) according to the first aspect, as described above, the plurality of detection chambers (10) are fluidly isolated from each other, and are connected via a passage (40) which functions as a light guide path. Therefore, it is possible to prevent the light (93) generated from the measurement sample (90) in a detection chamber (10) from being propagated to another detection chamber (10) via the passage (40). The amount of transmission light (91) passing through the inside of the cartridge (100) toward the other detection chamber (10) among the light generated from the measurement sample (90) in the detection chamber (10) can be reduced in the process of passing through the transmission suppression unit (20) since the transmission suppression unit (20) is provided between each of the plurality of detection chambers (10). As a result, light generated in each detection chamber (10) can be suppressed from being mixed into another detection chamber (10) since it is possible to suppress both the propagation of light through the passage and the propagation of light (91) passing through the inside of the cartridge (100) toward another detection chamber (10).

In the cartridge (100) according to the first aspect, the transmission suppression unit (20) preferably includes a light absorbing part (21) for absorbing light generated from the measurement sample (90), and a light scattering part (22) for scattering light generated from the measurement sample (90). According to the configuration in which the transmission suppression unit (20) includes the light absorbing part (21), the transmission of the light (91) incident on the transmission suppression unit (20) among the light generated from the measurement sample (90) can be suppressed by absorption by the light absorbing part (21). It also is possible to prevent the light (91) incident on the transmission suppression unit (20) from being scattered toward the external light detecting unit. According to the configuration in which the transmission suppression unit (20) includes the light scattering part (22), the light (91) incident on the transmission suppressing unit (20) among the light generated from the measurement sample (90) can be prevented from reaching another detection chamber (10) direction of scatter via the light scattering part (22). Note that in this specification, the term “scattering light” means that light changes its direction when it enters an object and is scattered; this is a broad concept that includes not only the scattering phenomenon of light incident on fine particles, but also reflection (including specular reflection and irregular reflection) on the material surface.

In the configuration in which the transmission suppression unit (20) includes at least one of the light absorbing part (21) and the light scattering part (22), it is preferable that the light absorbing part (21) includes a light absorbing filler that absorbs the light generated from the measurement sample (90). According to this configuration, the transmission suppression unit (20) that includes the light absorbing part (21) can be easily provided in the cartridge (100) just by mixing the light absorbing filler into the base material such as a resin material. The light transmittance of the transmission suppression unit (20) can be controlled to a desired value just by adjusting the content of the light absorbing filler.

In the configuration in which the transmission suppression unit (20) includes at least one of the light absorbing part (21) and the light scattering part (22), it is preferable that the light scattering part (22) includes a light scattering filler that scatters light generated from the measurement sample (90), as shown inFIG.4. According to this configuration, the transmission suppression unit (20) including the light scattering part (22) can be easily provided in the cartridge (100) just by mixing the light scattering filler with a base material such as a resin material. The light transmittance of the transmission suppression unit (20) also can be controlled to a desired value simply by adjusting the light scattering filler content.

In the cartridge (100) according to the first aspect, preferably, the cartridge (100) has a flat plate-like shape, the plurality of detection chambers (10) extend along the surface of the cartridge (100), and the transmission suppression unit (20) has a light transmittance of 30% or less of light generated from the measurement sample (90), as shown inFIG.7. When a plurality of detection chambers (10) are provided along the surface of the flat cartridge (100) in this manner, it is possible to ensure a sufficiently low light transmittance between the detection chambers (10), just by, for example, providing a transmission suppression unit (20) with a width at least equal to or greater than the thickness of the cartridge (100) between the plurality of detection chambers (10). Therefore, it is possible to effectively prevent light generated in one of the plurality of detection chambers (10) from being mixed into another detection chamber (10). Note that in the present specification, “transmittance of light generated from the measurement sample (90)” means light transmittance of a peak wavelength of light generated from the measurement sample (90).

In the cartridge (100) according to the first aspect, light generated from the measurement sample (90) may be light having a wavelength of 300 nm or more and 800 nm or less, as shown inFIG.6. The light having a wavelength of 300 nm or more and 800 nm or less includes peak wavelengths of various luminescent substances used for labeling a test substance obtained from a biological sample. Therefore, it is suitable for the cartridge (100) used for detecting a test substance obtained from a biological sample.

In the cartridge (100) according to the first aspect, preferably, the light generated from the measurement sample (90) is light generated by chemiluminescence, as shown inFIG.8. Chemiluminescence is a phenomenon in which energy is emitted as light when a molecule excited by a chemical reaction returns to a ground state. In chemiluminescence, for example, light emission continues once emission is started unlike fluorescence in which light emission can be controlled by turning on and off excitation light. Therefore, the above-mentioned cartridge (100) capable of suppressing the mixing of the light (91) between the detection chambers (10) is particularly useful since emission of light in another detection chamber (10) cannot be stopped while light detection is being performed in any of the plurality of detection chambers (10) in the case of chemiluminescence. In this way the S/N ratio in light detection can be improved, so that the detection accuracy of the test substance can be improved.

In this case, preferably, a plurality of liquid storage units (67) corresponding to the plurality of detection chambers (10) and fluidly connected to the plurality of detection chambers are provided, respectively, and each of the plurality of liquid containers (67) is configured such that a luminescent substrate is disposed therein, as shown inFIG.7. According to this configuration, the chemiluminescence of the measurement sample (90) can be generated inside the detection chamber (10) just by transferring the luminescent substrate from the liquid container (67) to the detection chamber (10). Therefore, unlike when a measurement sample (90) to be luminesced is transferred from a unit other than the detection chamber (10), the region in which light is generated can be limited to just the inside of the detection chamber (10), such that it is possible to increase the sensitivity of the photodetection using the cartridge (100).

In the cartridge (100) according to the first aspect, it is preferable that each of the plurality of detection chambers (10) continues to store the measurement sample (90) for which light detection by the detection device has been completed, as shown inFIG.7. According to this configuration, the measurement sample (90) after the light detection is completed is kept stored inside the detection chamber (10), and the luminescent measurement sample (90) can be prevented from being transported outside the detection chamber (10). The light generated from the measurement sample (90) can be reliably made incident on the transmission suppression unit (20) since the measurement sample (90) is not transferred to the outside of the detection chamber (10). Therefore, when, for example, the light detection in each of the plurality of detection chambers (10) is performed in order, the light given off from the moved measurement sample (90) due to the movement of the measurement sample (90) whose light detection has been completed first can be prevented from reaching another detection chamber (10).

In the cartridge (100) according to the first aspect, it is preferable that the cartridge (100) has a flat plate-like shape that is rotated around a rotation axis (321), and includes a plurality of detection chambers (10) arranged at a position on the outer peripheral side of the cartridge (100) about the rotation axis (321), as shown inFIG.7. According to this configuration, a liquid can be sent to the detection chamber (10) using the centrifugal force generated when the cartridge (100) is rotated. At this time, a large distance between the detection chambers (10) in the cartridge (100) can be ensured since the plurality of detection chambers (10) are arranged at positions on the outer peripheral side of the cartridge (100), compared with when the plurality of detection chambers (10) are arranged on the inner peripheral side of the cartridge (100). As the distance between the detection chambers (10) increases, the arrival of the light (91) between the detection chambers (10) is suppressed, so that the light generated in each of the plurality of detection chambers (10) is effectively suppressed from being transmitted to the other detection chambers (10).

In the cartridge (100) according to the first aspect, the cartridge (100) preferably has a flat plate-like shape that is rotated around a rotation axis (321), and includes a plurality of detection chambers (10) arranged at angular intervals obtained by equally dividing one rotation around the rotation axis (321), as shown inFIG.7. According to this configuration, the distance between the adjacent detection chambers (10) can be as large as possible in the cartridge (100). As the distance between the detection chambers (10) increases, the arrival of the light (91) between the detection chambers (10) is suppressed, so that the light generated in each of the plurality of detection chambers (10) is effectively suppressed from being transmitted to the other detection chambers (10).

In the cartridge (100) according to the first aspect, it is preferable that a plurality of processing regions (60) respectively further comprising a plurality of processing regions (60) each including one detection chamber included in the plurality of detection chambers, and a passage (40) for transferring a test substance to the one detection chamber (10), wherein the transmission suppression unit (20) is provided so as to isolate one processing region from the other processing regions in the plurality of processing regions (60). According to this configuration, the transmission of the light generated from the measurement sample (90) between the plurality of processing regions (60) can be suppressed by the transmission suppression unit (20). As described above, the light (93) generated from the measurement sample (90) propagates through the passage (40) into the processing region (60) connected to the detection chamber (10) via the passage (40). Therefore, since the transmission suppression unit (20) is provided between the processing regions (60) according to the above configuration, light can be reliably made incident on the transmission suppression unit (20) to reduce the amount of transmitted light even when light (93) propagated into a processing region (60) other than the detection chamber (10) via the passage (40) passes through the inside of the cartridge (100) and travels to another detection chamber (10). As a result, the light (93) propagated into a processing region (60) other than the detection chamber (10) via the passage (40) can be effectively prevented from reaching another detection chamber (10).

In the cartridge (100) according to the first aspect, the cartridge (100) preferably has a flat plate-like shape that is rotated around a rotation axis (321), as shown inFIGS.7and17, and the transmission suppression unit (20) is continuously provided from the rotation shaft (321) or the end part (54a) of the cartridge on the rotation shaft (321) side to the end part (54b) of the cartridge on the side distant from the rotation shaft (321). According to this configuration, the transmission suppression unit (20) can be provided continuously from end to end so as to radially divide the cartridge (100) between the plurality of detection chambers (10). Therefore, the light (91) directed to another detection chamber (10) among the light generated from the measurement sample (90) can be reliably made to enter the transmission suppression unit (20), such that the light generated from the measurement sample (90) can be effectively suppressed from reaching another detection chamber (10).

The cartridge (100) according to the first aspect preferably further includes, a wall (51) that partitions each of the plurality of detection chambers (10) as shown inFIGS.7and8, wherein the transmission suppression unit (20) includes the wall (51), and each of the plurality of detection chambers (10) has a light extraction unit (11) that is not covered by the wall (51). According to this configuration, since the wall (51) itself, which is a structural part of the cartridge (100), can be configured by the transmission suppression unit (20), the amount of transmitted light incident into the cartridge (100) can be reliably and effectively reduced. Even in this case, light generated from the measurement sample (90) in the detection chamber (10) can be detected with high accuracy since light is radiated to the outside of the cartridge (100) from the light extraction unit (11) not covered with the wall (51) in each detection chamber (10).

In this case, it is preferable that a flat plate-like main body (50) including a plurality of detection chambers (10) and a wall (51), and a cover (52) which covers at least a part of the main body (50) and has a light transmittance higher than that of the wall (51) in a thickness direction of the main body (50) are further provided, wherein each of the plurality of detection chambers (10) has a structure in which a through-hole or a non-penetrating recess provided in the wall (51) of the main body (50) is covered with the cover (52). According to this configuration, the detection chamber (10) having the light extraction unit (11) can be easily obtained by simply covering the through hole or the non-penetrating recess provided in the wall (51) of the main body (50) with the cover (52).

In the cartridge (100) in which the wall (51) is configured by the transmission suppression unit (20), the wall (51) preferably a plurality of passages (40) fluidly connected to the plurality of detection chambers (10) are provided so as to correspond to the plurality of detection chambers (10) as shown inFIGS.7and9, respectively, and the transmission suppression unit (20) is configured to transmit at least part of the light directed in the thickness direction of the cartridge (100) in the formation region of each of the plurality of passages (40). According to this configuration, the inside of the formation region of the passage (40) can be optically viewed or photographed even when the wall (51) is formed by the transmission suppression unit (20). Therefore, it is possible to externally determine whether the transfer of a liquid such as the sample or the reagent in the passage (40) is appropriate. In this way the reliability of the detection accuracy of the test substance can be ensured if the detection process is appropriate by externally evaluating whether the detection process of the test substance using the cartridge (100) is appropriate. Therefore, the reliability of the detection accuracy of the test substance can be easily confirmed from the appearance of the cartridge (100) even when the wall (51) is configured by the transmission suppression unit (20).

In this case, it is preferable that a plurality of processing chambers (61to65) are provided corresponding to the plurality of detection chambers (10) and fluidly connected to the plurality of detection chambers (10) through corresponding passages (40) as shown inFIG.7, wherein the transmission suppression unit (20) is configured to transmit at least a part of light traveling in the thickness direction of the cartridge (100) in each of the formation regions of the plurality of processing chambers (61to65). According to this configuration, whether the processing of the test substance in the processing chambers (61to65) is appropriate can be grasped from the outside, similar to the passage (40). Therefore, the reliability of the detection accuracy of the test substance can be easily confirmed from the appearance of the cartridge (100) even when the wall (51) is configured by the transmission suppression unit (20).

The cartridge (100) according to the first aspect preferably also includes, as shown inFIGS.17and18, a wall (51) for partitioning each of the plurality of detection chambers (10), wherein the transmission suppression unit (120) is configured by a member partially formed on the surface or inside of the wall (51). According to this configuration, for example, a layer of the transmission suppression unit (120) is formed on the surface of the wall (51), or the transmission suppression unit (120) is embedded in a part of the wall (51), so as to dispose the transmission suppression unit (120) locally. In this way the transmission suppression unit (120) can be provided while securing freedom in selecting the constituent material of the wall (51). For example, the transmission of light can be more effectively suppressed by a plurality of types of transmission suppression units (120) when the wall (51) is configured by the first transmission suppression unit (20) and the second transmission suppression unit (120) is provided on the surface or inside of the wall (51).

The detection method according to a second aspect of the present invention is a detection method using a cartridge (100) having a plurality of detection chambers (10) as shown inFIGS.1and2, wherein light (92) emitted from a measurement sample contained in one detection chamber (10) in a second direction (DR2) different from the first direction (DR1) is detected while transmission of light (91) emitted from the measurement sample included in one detection chamber toward the other detection chamber is suppressed in the first direction (DR1) by a transmission suppression unit (20) provided between one detection chamber and another detection chamber of the plurality of detection chambers (10) fluidly isolated from each other.

In the detection method according to the second aspect described above, the plurality of detection chambers (10) are fluidly isolated from each other in the cartridge (100), and are not connected via the passage (40) functioning as a light guide path. Therefore, it is possible to prevent light (93) generated from the measurement sample (90) in one detection chamber (10) from being propagated to another detection chamber (10) via the passage (40). Regarding the light (91) in a first direction (DR1) passing through the inside of the cartridge (100) toward another detection chamber (10) of the light generated from the measurement sample (90) in one detection chamber (10), it is to be noted that the amount of transmitted light can be reduced in the process of passing through the transmission suppression unit (20) by the transmission suppression unit (20) provided between each of the plurality of detection chambers (10). Then, the light (92) emitted in the second direction (DR2) different from the first direction (DR1) can be detected. As a result, both the propagation of light through the passage and the propagation of light (93) passing through the interior of the cartridge (100) toward the other detection chamber (10) can be suppressed, so that it is possible to suppress the light generated in one detection chamber (10) from being mixed into another detection chamber (10).

In the detection method according to the second aspect, it is preferable in the step of detecting light, when light is generated from a measurement sample (90) included in one detection chamber (10), the light generated from a measurement sample (90) contained in another detection chamber (10) is detected, as shown inFIG.13. According to this configuration, the light is not generated from the measurement samples (90) in the plurality of detection chambers (10) sequentially with a time lag, but rather the light is simultaneously emitted from each of the plurality of detection chambers (10). Therefore, the processing of the measurement samples (90) does not need to be performed in order, and the processing time required to detect light generated from the measurement sample (90) in each of the plurality of detection chambers (10) can be reduced. Also in this case, the transmission suppression unit (20) provided in the cartridge (100) can perform high-precision light detection in which light is prevented from being mixed into the plurality of detection chambers (10).

In the detection method according to the second aspect, it is preferable that the cartridge (100) is disposed in a light-shielded housing (310) which absorbs light as shown inFIG.13, and the method further includes a step of suppressing scattering of light emitted from the inside of the cartridge (100) to the outside by the inner surface (315) of the cartridge (100). According to this configuration, among the light generated from the measurement sample (90) emitted to the outside of the cartridge (100), the light traveling in a direction other than the second direction (DR2) impinges the inner surface (315) of the housing (310) and is absorbed by the inner surface (315) of the housing (310). As a result, it is possible to prevent light traveling in a direction other than the second direction (DR2) from being scattered within the housing (310) and mixed into another detection chamber (10).

In a cartridge including a plurality of detection chambers, light generated in one of the plurality of detection chambers can be prevented from being mixed into another detection chamber.

DESCRIPTION OF THE EMBODIMENTS

Summary of Cartridge

The cartridge100according to the present embodiment will be described with reference toFIG.1.

The cartridge100is installed in a detection device300for detecting light generated from the measurement sample90containing a test substance, and is used for detecting light generated from the measurement sample90.

The test substance is, for example, a substance contained in a sample collected from a human subject. The sample maybe blood (whole blood, serum or plasma), urine, tissue fluid, or other body fluid, or a liquid obtained by subjecting a collected body fluid or blood to a predetermined pretreatment. The sample includes a liquid as a main component and may include a solid component such as cells. The test substance can be, for example, proteins such as antigens or antibodies, peptides, cells and intracellular substances, nucleic acids such as DNA (deoxyribonucleic acid).

The measurement sample90includes a test substance and a substance that emits light. The test substance itself may be a substance that generates light. The measurement sample90contains a liquid as a main component. The measurement sample90may be a mixture of a test substance and a reagent. The reagent emits light, for example, according to the amount of the test substance. The luminescence is, for example, chemiluminescence or fluorescence. The reagent contains, for example, a labeling substance that specifically binds to the detection target substance. The labeling substance can be a chemiluminescent or fluorescent substance. For example, the labeling substance includes an enzyme, and the reagent includes a luminescent substrate that reacts with the enzyme. By detecting the light generated from the measurement sample90, the presence or absence of the test substance, the amount or concentration of the test substance, and the size and shape of the particulate test substance can be measured according to the measurement item. The type of reagent mixed with the measurement sample90differs depending on the measurement item. There may be a plurality of types of variations of the cartridge100for each measurement item. The cartridge100may be capable of measuring a plurality of different measurement items.

The detection device300includes a photodetector331such as a photomultiplier tube, a phototube, and a photodiode. When the cartridge100is installed in the detection device300, light from the measurement sample90is detected by the detection device300. The photodetector331detects light from outside the cartridge100installed in the detection device300. The detection device300can be configured to act from outside the cartridge100to perform processing for preparing the measurement sample90inside the cartridge100. The process of preparing the measurement sample90includes generating a measurement sample90that emits light in the cartridge100by performing contact, agitation, temperature adjustment, and the like on the sample containing the test substance via a reagent. The configuration may be such that the measurement sample90prepared so as to generate light is injected into the cartridge100.

The cartridge100is a replaceable consumable. That is, the cartridge100is discarded after being used for measurement a preset number of times. The usable number of times of the cartridge100is one or several times. The cartridge is a replaceable part that performs functions necessary for detecting a test substance contained in a sample.

The cartridge100includes at least an opening for introducing a liquid containing the test substance, and a space capable of containing the liquid containing the test substance.

InFIG.1, the cartridge100includes an inlet30for introducing a sample. The inlet30is, for example, an opening formed on the outer surface of the cartridge100. The opening serving as the inlet30may be closed in advance, in which case the cartridge100is opened by an operator when the cartridge100is used. The inlet30receives a liquid containing a specimen. The inlet30can receive a measurement sample90which is a mixture of a reagent for treating a test substance and a specimen.

The cartridge100includes a chamber capable of storing a liquid therein. The chamber may be a substantially closed space so that liquid does not leak inside the cartridge100. The substantially closed space is a space permitted to communicate with the outside of the cartridge100via the inlet30and a path for discharging gas in the chamber with the introduction of the liquid into the chamber. The chamber may be configured such that the liquid in the chamber does not flow back to the inlet30under normal use conditions.

The cartridge100of the present embodiment includes at least a plurality of detection chambers10. The plurality of detection chambers10are configured to receive the measurement sample90and to detect light generated from the received measurement sample90by the photodetector331. Each detection chamber10has a volume that can accommodate at least the measurement sample90prepared to emit light. Each detection chamber10is in communication with the inlet30via a passage40. The number of detection chambers10is not particularly limited insofar as it is plural. In the example ofFIG.1, the cartridge100includes two detection chambers10.

In the present embodiment, the plurality of detection chambers10are fluidly isolated from each other. That is, the plurality of detection chambers10are structurally provided in the same cartridge100, but are not connected to each other via the passage40. Note that the fluid is specifically a liquid, and “fluidly isolated” means that the fluids are not connected via a liquid-passable passage. No liquid flows between the plurality of detection chambers10. Therefore, in the cartridge100ofFIG.1, a plurality of inlets30and a plurality of passages40are separately provided for each of the plurality of detection chambers10. The plurality of detection chambers10are isolated from each other by a structural material of the cartridge100. That is, each detection chamber10is a space divided by the wall51, and the plurality of detection chambers10are isolated from each other by the wall51.

The passage40is a tubular space formed inside the cartridge100. The passage40can transfer the liquid so as to pass through the inside thereof by, for example, pressure such as air pressure, gravity, centrifugal force, or other inertial force.

In the present embodiment, the cartridge100includes the transmission suppression unit20provided between each of the plurality of detection chambers10. The transmission suppression unit20is configured to suppress transmission of light generated from the measurement sample90in a detection chamber10to another detection chamber10.

The transmission suppression unit20is provided, for example, inside the cartridge100. The transmission suppression unit20is provided, for example, on the inner surface of the detection chamber10. The transmission suppression unit20is arranged at least on a straight line connecting the plurality of detection chambers10to each other.

As shown inFIG.1, light generated from a measurement sample90disposed in the detection chamber10is emitted in all directions. Therefore, light generated from the measurement sample90is emitted in a first direction DR1that connects each of the plurality of detection chambers10to each other. The transmission suppression unit20is disposed in the first direction DR1for each detection chamber10.

Therefore, the light91in the first direction DR1generated from the measurement sample90in any one of the plurality of detection chambers10passes through the inside of the cartridge100and enters the transmission suppression unit20before reaching another detection chamber10. The transmission suppression unit20reduces the amount of transmitted light passing through the transmission suppressing unit20at least by the amount of incident light91. Therefore, the amount of light generated in one of the detection chambers10that passes through the transmission suppression unit20and reaches another detection chamber10is reduced. Note that the amount of transmitted light is the amount of transmitted light that enters the transmission suppression unit20, passes directly through the transmission suppression unit20, and exits from the transmission suppression unit20. The amount of light may be alternatively referred to as the number of photons.

Light generated from the measurement sample90is also emitted in a second direction DR2different from the first direction DR1. The photodetector331of the detection device300detects the light92emitted from each detection chamber10of the cartridge100installed in the detection device300in the second direction DR2different from the first direction DR1. That is, the photodetectors331are arranged at positions other than the first direction DR1relative to each detection chamber10in a state where the cartridge100is installed in the detection device300. The photodetector331outputs a signal corresponding to the amount of detected light92or the number of photons.

The light emitted from the measurement sample90includes, in addition to the first direction DR1and the second direction DR2, light93emitted toward the inside of the passage40. Since the passage40is a space defined by the structural materials of the cartridge100, the light93emitted into the passage40may be reflected on the inner surface of the passage40and propagate along the passage40. That is, the passage40may act as a light guide path exemplified by an optical fiber.

For example, as shown by the two-dot chain line inFIG.1, when a common passage CP connecting each of the plurality of detection chambers10is provided, light93generated inside any one of the detection chambers10may propagate along the path CP and reach another detection chamber10. Since the transmission suppression unit20cannot be formed so as to block the passage CP which is a space, the propagation of the light93in the passage CP cannot be suppressed by the transmission suppression unit20. In the present embodiment, however, each of the detection chambers10is fluidly isolated and is not connected via the passage40. Therefore, the light93reaching another detection chamber10through the passage40is prevented even if the light93generated inside one of the detection chambers10propagates along the passage40.

As described above, when detecting the light92generated from the measurement sample90in one of the detection chambers10, the light91in the first direction DR1emitted from another detection chamber10and the light93propagating through the passage40are prevented from reaching the detection chamber10as extraneous light.

In the cartridge100according to the present embodiment described above, the plurality of detection chambers10are fluidly isolated from each other, and are not connected through the passage40that acts as a light guide path. Therefore, it is possible to prevent the light93generated from the measurement sample90in a detection chamber10from being propagated to another detection chamber10via the passage40. Regarding the light91that passing through the inside of the cartridge100to another detection chamber10among the light generated from the measurement sample90in a given detection chamber10, the amount of transmitted light can be reduced in the process of passing through the transmission suppression unit20since the transmission suppression unit20is provided between each of the plurality of detection chambers10. As a result, since both the propagation of the light93through the passage40and the propagation of the light91passing through the inside of the cartridge100toward another detection chamber10can be suppressed, it is possible to suppress the generated light from being mixed into another detection chamber10.

Detection Method

Next, a detection method according to the present embodiment will be described. The detection method according to the present embodiment is a detection method for detecting light generated from the measurement sample90using a cartridge100including a plurality of detection chambers10for receiving the measurement sample90containing the test substance. The detection method according to the present embodiment can be performed by the detection device300that detects light using the cartridge100.

The detection device300is a detection device that uses a cartridge100having a plurality of detection chambers10to detect a test substance contained in a sample injected into the cartridge100. The detection device300is, for example, a small-sized detection device for PoC (Point of Care) examination, and is configured to be able to execute a measurement operation by a simple operation.

The detection device300includes a photodetector331that detects light92generated from the measurement sample90in the detection chamber10. The detection device300measures, for example, the presence or absence of a test substance, the amount or concentration of the test substance and the like based on the output signal of the photodetector331.

As shown inFIG.2, the detection method of the present embodiment includes at least the following steps S1and S2. (S1) The measurement sample90is placed in each of the plurality of detection chambers10that are fluidly isolated from each other. (S2) While the transmission suppression unit20provided between each of the plurality of detection chambers10suppresses the transmission of light91generated from the measurement sample90radiated in the first direction DR1, the light92generated from the measurement sample90emitted in the second direction DR2different from the first direction DR1is detected for each of the plurality of detection chambers10.

In step S1, the measurement sample90can be arranged in each of the detection chambers10by a function of the detection device300. The arrangement of the measurement sample90includes preparation of the measurement sample90in the detection chamber10by transferring the test substance and the reagent into the detection chamber10, respectively. A measurement sample90prepared in advance also may be introduced into the cartridge100. As a result of step S1, light generated from the measurement sample90is emitted from each of the detection chambers10in various directions.

In step S2, light emitted from each of the plurality of detection chambers10is detected by the photodetector331. At this time, the transmission of the light91radiated in the first direction DR1in the cartridge100is suppressed by the transmission suppression unit20. Since each of the plurality of detection chambers10is fluidly isolated, light93emitted into the passage40of the cartridge100is prevented from reaching another detection chamber10. Then, light92emitted from the measurement sample90and emitted in the second direction DR2which is different from the first direction DR1is detected by the photodetector331. When detecting the light92, the light92emitted from each of the plurality of detection chambers10may be simultaneously detected by a plurality of photodetectors331in parallel. In this case, the detection device300may include a plurality of photodetectors331. When detecting the light92, the light92emitted from each of the plurality of detection chambers10also may be sequentially detected by the same light detector331. In this case, the detection device300may be provided with a mechanism for relatively moving the cartridge100and the photodetector331, or a light guide mechanism that can individually switch between guiding and blocking light emitted from each detection chamber10to the photodetector331.

As described above, in the detection method of the present embodiment, the plurality of detection chambers10in the cartridge100are fluidly isolated from each other, and are not connected via the passage40that acts as a light guide path. Therefore, it is possible to prevent the light93generated from the measurement sample90in a detection chamber10from being propagated to another detection chamber10via the passage40. Then, regarding the light91in the first direction DR1that passes through the inside of the cartridge100and travels to the other detection chambers10among the light generated from the measurement sample90in the detection chamber10, the amount of light can be reduced in the process of passing through the transmission suppression unit20by the transmission suppression unit20provided between each of the plurality of detection chambers10. Then, the light92emitted in the second direction DR2which is different from the first direction DR1can be detected. As a result, since both the propagation of the light93through the passage40and the propagation of the light91passing through the inside of the cartridge100toward another detection chamber10can be suppressed, it is possible to suppress the generated light from being mixed into another detection chamber10.

In the example shown inFIG.1, when light from the measurement sample90is generated from each of a plurality of detection chambers10, light92generated from the measurement sample90of each of the plurality of detection chambers10is detected. That is, the measurement sample90in a state of generating light is simultaneously placed in each of the plurality of detection chambers10. Therefore, the light is emitted from each of the plurality of detection chambers10at the same time, and the photodetectors331individually detect the light92emitted from each of the plurality of detection chambers10.

According to this configuration, light can be simultaneously generated from each of the plurality of detection chambers10rather than sequentially generating light from the measurement sample90with a time lag. Therefore, the processing of the measurement sample90does not need to be performed in order, and the processing time required to detect the light92generated from the measurement sample90in each of the plurality of detection chambers10can be reduced. Also in this case, high-precision light detection can be performed in which light is prevented from being mixed into the plurality of detection chambers10by the transmission suppression unit20provided in the cartridge100.

Transmission Suppression Unit

The structure of the transmission suppression unit20is not particularly limited insofar as the transmission of the light91in the first direction DR1from one of the detection chambers10to another detection chamber10among the light generated from the measurement sample90can be suppressed. The transmission suppression unit20suppresses the transmission of the light91by absorbing the light91, for example. The transmission suppression unit20suppresses the transmission of the light91by, for example, scattering the light91.

For example, as shown inFIGS.3to5, the transmission suppression unit20may include at least one of a light absorbing part21that absorbs light generated from the measurement sample90, and a light scattering part22that scatters light generated from the measurement sample90. According to the configuration in which the transmission suppression unit20includes the light absorption unit21, the light91incident on the transmission suppression unit20among the light generated from the measurement sample90is absorbed by the light absorbing part21to suppress the transmission of the light. It also is possible to suppress the light91incident on the transmission suppression unit20from being scattered toward the external photodetector unit. According to the configuration in which the transmission suppression unit20includes the light scattering part22, the light91incident on the transmission suppression unit20among the light generated from the measurement sample90is scattered by the light scattering part22to change the direction of the light such that the light is prevented from reaching another detection chamber10.

In the example ofFIG.3, the transmission suppression unit20includes a light absorbing part21that absorbs light generated from the measurement sample90. When light generated from the measurement sample90enters the light absorbing part21of the transmission suppression unit20, the incident light91is absorbed by the light absorbing part21. As a result, transmission of light generated from the measurement sample90is suppressed in the transmission suppression unit20.

In the example ofFIG.3, the light absorbing part21includes a light absorbing filler that absorbs light generated from the measurement sample90. The transmission suppression unit20has a structure in which a light absorbing filler is dispersed in a base material such as a resin material, for example. The light absorbing filler is fine particles of a pigment that absorbs light. Light absorbing fillers include inorganic pigments and organic pigments. Examples of the inorganic pigment include oxides and composite oxides of inorganic materials such as carbon black and iron.

In this way the transmission suppression unit20incorporating the light absorbing part21can be easily provided in the cartridge100just by mixing the light absorbing filler into a base material such as the resin material. The light transmittance of the transmission suppression unit20also can be controlled to a desired value just by adjusting the light absorbing filler content.

Note that the light absorbing part21may be a layer formed of a light absorbing material instead of the light absorbing filler. In this case, the light absorbing part21is formed by forming a film on the cartridge100, and configures the transmission suppression unit20.

In the example ofFIG.4, the transmission suppression unit20includes a light scattering part22that scatters light generated from the measurement sample90. When light generated from the measurement sample90enters the light scattering part22of the transmission suppression unit20, the incident light91is scattered by the light scattering part22. Due to the scattering, the traveling direction of the light91changes. The transmission suppression unit20diffuses light generated from the measurement sample90in random directions by, for example, scattering. As a result, the light91emitted from one of the detection chambers10is suppressed from passing through the transmission suppression unit20and reaching another detection chamber10.

In the example ofFIG.4, the light scattering part22includes a light scattering filler that scatters light generated from the measurement sample90. The transmission suppression unit20has a structure in which a light scattering filler is dispersed in a base material such as a resin material. Light scattering fillers are fine particles of a substance that scatters light. Light scattering fillers include inorganic particles and organic particles. Examples of the inorganic particles include calcium carbonate and titanium oxide. Examples of the organic particles include acrylic particles, silicone particles, and styrene particles having high crystallinity.

In this way the transmission suppression unit20incorporating the light scattering part22can be easily provided in the cartridge100just by mixing the light scattering filler with a base material such as the resin material. The light transmittance of the transmission suppression unit20also can be controlled to a desired value just by adjusting the light scattering filler content.

Note that the light scattering part22also may be a layer formed of a light scattering material instead of the light scattering filler, as shown inFIG.5. In this case, the light scattering part22is formed by forming a film on the cartridge100, and configures the transmission suppression unit20. The layer of the light scattering part22can diffusely or specularly reflect light generated from the measurement sample90(seeFIG.5).

Light Wavelength

The transmission suppression unit20only needs to suppress transmission of light generated from the measurement sample90, and does not need to suppress transmission of light other than light generated from the measurement sample90. In other words, the transmission suppression unit20only needs to suppress transmission of at least the wavelength component of light generated from the measurement sample90. Therefore, for example, a black pigment such as carbon black is exemplified as the above-described light-absorbing filler, but it does not need to be black. Since black pigment has a flat light absorption characteristic that does not depend on the specific light wavelength, it is preferable in that the wavelength of light generated from the measurement sample90can be selected in a wide range.

Specifically, light generated from the measurement sample90is light having a wavelength of 300 nm or more and 800 nm or less. The light having a wavelength of 300 nm or more and 800 nm or less includes peak wavelengths of various luminescent substances used for labeling a test substance obtained from a biological sample. Therefore, it is suitable for the cartridge100used for detecting a test substance obtained from a biological sample.

The light generated from the measurement sample90is, for example, chemiluminescence. In chemiluminescence, for example, light emission continues once emission is started unlike fluorescence in which light emission can be controlled by turning on and off excitation light. Therefore, in the case of chemiluminescence, light emission in another detection chamber10cannot be stopped while light detection is being performed in any of the plurality of detection chambers10, such that the cartridge100capable of suppressing light from being mixed in the cartridge is particularly useful. In this way the S/N ratio in light detection can be improved, so that the detection accuracy of the test substance can be improved.

FIG.6is an example of a spectrum SP of light generated from the measurement sample90. InFIG.6, the vertical axis indicates the light emission amount, and the horizontal axis indicates the wavelength of light.FIG.6shows, as an example, a chemiluminescence spectrum SP of CDP-Star (registered trademark) which is a dioxetane-based luminescent substrate used in a chemiluminescence immunoassay. CDP-Star (registered trademark) is a chemiluminescent substrate for the enzyme alkaline phosphatase (ALP). In the spectrum SP ofFIG.6, the peak wavelength of light generated from the measurement sample90is about 450 nm. In the spectrum SP ofFIG.6, the light generated from the measurement sample90has a wavelength range from about 350 nm to about 650 nm.

Although the transmission suppression unit20does not need to completely suppress the transmission of the light91that is generated from the measurement sample90in one of the detection chambers10and travels to another detection chamber10, it is desirable to sufficiently suppress the transmission. The transmission suppression unit20may be configured to substantially block transmission of the light91in the first direction DR1between the plurality of detection chambers10. In other words, the transmission suppression unit20is configured of a translucent or opaque material. It is preferable that the light transmittance of the transmission suppression unit20with respect to the light91generated from the measurement sample90is a sufficiently low value of 0% or more. Here, the light transmittance of the transmission suppression unit20with respect to the light generated from the measurement sample90means the light transmittance at the peak wavelength of the light generated from the measurement sample90.

The ratio of the amount of light reaching the detection chamber10that performs light detection from another detection chamber10through the transmission suppression unit20is set to be below a reference value relative to the light transmittance of the transmission suppression unit20based on the amount of light emitted in the detection chamber10that performs light detection. The reference value can be, for example, 1/103, 1/104, 1/105, 1/106, 1/(2×106), 1/(5×106), 1/107, or the like.

Example of Specific Cartridge Configuration

Next, a specific configuration example of the cartridge100will be described. In the example ofFIG.7, the cartridge100has a flat plate-like shape. The cartridge100is rotated around a rotation shaft321. Specifically, the cartridge100is a disk-type cartridge formed of a plate-shaped, that is, disk-shaped substrate. In the example shown inFIG.7, the cartridge100is configured as a sample processing cartridge capable of executing a process for detecting a test substance in a sample using an antigen-antibody reaction.

In the example ofFIG.7, the cartridge100includes three detection chambers10that are fluidly isolated from each other.

In the example ofFIG.7, the cartridge100includes a wall51that partitions the plurality of detection chambers10. In the example ofFIG.7, the wall51is configured by the transmission suppression unit20. In the example ofFIG.7, the entirety of the wall51that partitions the spaces that form the various chambers and passages of the cartridge100is configured by the transmission suppression unit20. Therefore, in the example ofFIG.7, the plurality of detection chambers10are fluidly isolated from each other by the transmission suppression unit20.

Specifically, as shown inFIG.8, the cartridge100includes a flat main body50including the plurality of detection chambers10and the wall51, and a cover52that covers at least a part of the main body50. The transmission suppression unit20including the light absorbing part21(seeFIG.3) that absorbs light generated from the measurement sample90is used as a structural material of the main body50including the wall51. In the configuration example ofFIG.8, the light absorbing part21(seeFIG.3) is a light absorbing filler that absorbs light generated from the measurement sample90. The transmission suppression part20is configured of a thermoplastic resin mixed with a light absorbing filler.

In the example ofFIG.7, the main body50has a thickness such that the temperature of the cartridge100can be easily adjusted by a heater361described later. For example, the thickness of the main body50is several millimeters, and specifically, about 1.2 mm. The diameter of the main body50is set to several centimeters to several tens cm in diameter, for example, about 12 cm.

The plurality of detection chambers10are arranged along the surface of the disk-shaped main body50. Each of the plurality of detection chambers10has the light extraction unit11that is not covered with the wall51in a direction other than the direction in which the plurality of detection chambers10face each other. The direction in which the plurality of detection chambers10face each other is the above-described first direction DR1(seeFIG.8). The direction other than the direction in which the plurality of detection chambers10face each other is the above-described second direction DR2(seeFIG.8). In the example ofFIG.7, each of the plurality of detection chambers10is open in the thickness direction of the disk-shaped main body50(that is, in the direction perpendicular to the paper surface ofFIG.7), and is not covered by the wall51, as shown inFIG.8. Therefore, the light extraction unit11is configured by the opening in the thickness direction.

With such a configuration, the wall51itself, which is a structural part of the cartridge100, can be configured by the transmission suppression unit20, so that the amount of transmitted light incident into the cartridge100can be reliably and effectively reduced. Even in this case, since the light92in the second direction DR2is emitted from the light extraction unit11not covered with the wall51to the outside of the cartridge100from within each detection chamber10, the light generated from the measurement sample90in the detection chamber10can be detected with high accuracy.

More specifically, each of the plurality of detection chambers10has a structure in which a through-hole or a non-penetrating recess provided in the wall51of the main body50is covered with a cover52. As shown inFIG.8, the detection chamber10is configured such that the through-holes formed in the main body50are covered by covers52on both surfaces of the main body50. The detection chamber10is a space defined by the wall51configuring the main body50and covers52on both sides in the thickness direction. The cover52has a light transmittance higher than that of the wall51with respect to the light of the measurement sample90in the thickness direction of the main body50. The light extraction unit11is configured by a portion of the cover unit52that covers the detection chamber10. In this way the detection chamber10provided with the light extraction unit11can be easily provided just by covering the through-hole or the non-penetrating recess provided in the wall51of the main body50with the cover52.

The cover52is configured by, for example, a light-transmitting film. The cover52preferably has a transparent portion covering the detection chamber10. The detection chamber10may be a non-penetrating recess formed in the main body50. In this case, instead of being provided on both surfaces of the main body50, the cover52covers the surface of the main body50on the side where the concave portion configuring the detection chamber10is open.

The cartridge100shown inFIG.7also is configured to receive a sample containing a test substance, and to process the sample inside the cartridge100so that a measurement sample90can be prepared. That is, the cartridge100shown inFIG.7includes a plurality of processing regions60including one detection chamber10and the passage40for transferring the test substance to the detection chamber10. In the example ofFIG.7, the cartridge100includes three processing regions60. Each of the three processing regions60includes one detection chamber10and the passage40.

The space of each of the three processing regions60is fluidly isolated from each other. Each of the three processing regions60is separately partitioned by the wall51that is the transmission suppression unit20. In other words, the transmission suppression unit20is provided so as to isolate the plurality of processing regions60from each other.

In this way the transmission suppression unit20can suppress the transmission of light generated from the measurement sample90between the plurality of processing regions60, which are regions connected to the detection chamber10and the passage40. As described above, the light generated from the measurement sample90can propagate through the passage40into the processing region60connected to the detection chamber10by the passage40. Therefore, according to the above configuration, since the transmission suppression unit20is provided between the processing regions60, the light93propagated through the passage40into the processing region60other than the detection chamber10is transmitted to the inside of the cartridge100, and when the light passes through the detection chamber10and goes to another detection chamber10, the light can be reliably made incident on the transmission suppression unit20to reduce the amount of transmitted light. As a result, the light93propagated through the passage40into the processing region60other than the detection chamber10can be effectively prevented from reaching another detection chamber10.

The plurality of processing regions60are provided so as to divide the main body50substantially equally. In the example ofFIG.7, three processing regions60are provided so as to divide the disk-shaped main body50into three equal parts in the circumferential direction. Each processing region60is formed as a fan-shaped area extending in a range of about 120 degrees from the center of the main body50.

The sample processing performed in the processing region60includes liquid transfer. In the configuration example ofFIG.7, the transfer of the liquid is performed by rotating the cartridge100about the rotation shaft321to apply a centrifugal force to the liquid. Therefore, the cartridge100has a flat plate-like shape that is rotated around a rotation shaft321. The cartridge100has a hole55passing through the main body50at the center of the main body50. The cartridge100is installed in the detection device300(seeFIG.10) such that the center of the hole55matches the center of the rotation shaft321.

The transmission suppression unit20is provided continuously from the rotation shaft321or the end on the rotation shaft321side to the end on the side away from the rotation shaft321. In the configuration example ofFIG.7, since the transmission suppression unit20is the wall51of the main body50, the transmission suppression unit20is continuously provided from the end54aon the rotation shaft321side to the end54bon the side remote from the rotation shaft321. The end54aon the rotation shaft321side is an inner peripheral surface of the hole55of the main body50. The end54bon the side away from the rotation shaft321is the outer peripheral surface of the main body50.

In this way the transmission suppression unit20can be provided continuously from end to end so as to divide the cartridge100in the radial direction between the plurality of detection chambers10. Therefore, the light91of the light generated from the measurement sample90directed to another detection chamber10can be reliably made to enter the transmission suppression unit20, so that the light generated from the measurement sample90can be effectively suppressed from reaching another detection chamber10. Note that a rotation shaft may be provided in the cartridge100instead of the hole55. In this case, the detection device300supports the rotation shaft of the cartridge100as a bearing. The transmission suppression unit20also may be provided continuously from the rotation shaft to an end on the side away from the rotation shaft321.

In addition, the plurality of detection chambers10are arranged around the rotation axis321at angular intervals obtained by equally dividing one rotation. In the configuration example ofFIG.7, the relative positions of the detection chambers10in each of the three processing regions60substantially match. Since the three processing regions60are provided so as to divide the disk-shaped main body50into three equal parts in the circumferential direction, the three detection chambers10are arranged at intervals of 120 degrees, each of which divides one rotation into three equal parts. In this way the distance between the adjacent detection chambers10in the cartridge100can be as large as possible. Since the arrival of the light91between the detection chambers10is suppressed as the distance between the detection chambers10increases, light generated in each of the plurality of detection chambers10can be effectively prevented from being mixed into other detection chambers10.

In the configuration example ofFIG.7, the plurality of detection chambers10are arranged at positions on the outer peripheral side of the cartridge100with the rotation shaft321as a center. In this way the liquid can be sent to the detection chamber10using the centrifugal force generated when the cartridge100is rotated. Since the plurality of detection chambers10are arranged on the outer peripheral side of the cartridge100, at this time a large distance between the detection chambers10in the cartridge100can be ensured compared to when the plurality of detection chambers10are arranged on the inner peripheral side of the cartridge100. Since the arrival of the light91between the detection chambers10is suppressed as the distance between the detection chambers10increases, light generated in each of the plurality of detection chambers10can be effectively prevented from being mixed into other detection chambers10. In the example ofFIG.7, a plurality of detection chambers10are arranged at the outermost periphery of the cartridge100. The arrangement at the outermost peripheral portion means that structures such as the passage40and other chambers are not arranged outside the detection chamber10.

In the configuration example ofFIG.7, the liquid sent to each of the plurality of detection chambers10by the rotation of the cartridge100is a luminescent substrate. That is, the cartridge100includes the liquid container67fluidly connected to each of the plurality of detection chambers10. The liquid container67is configured such that a luminescent substrate for generating light from the measurement sample90is disposed therein. Therefore, a luminescent substrate is sent to each of the detection chambers10from each of the corresponding liquid storage units67. A measurement sample90that emits chemiluminescence is prepared in the detection chamber10as a result of sending the luminescent substrate.

In this way the chemiluminescence of the measurement sample90can be generated only inside the detection chamber10by transferring the luminescent substrate from the liquid container67to the detection chamber10. Therefore, unlike when the luminescent measurement sample90is transferred from a portion other than the detection chamber10, the region where light is generated can be limited to only the inside of the detection chamber10, and the detection sensitivity using the cartridge100can be increased.

Note that the luminescent substrate is arranged in the liquid storage unit67in advance when the cartridge100is manufactured. The luminescent substrate also may be injected into the empty liquid container67by the user when the cartridge100is used.

In the configuration example ofFIG.7, the plurality of detection chambers10also are spaced apart along the surface of the cartridge100. The distance between each of the plurality of detection chambers10is greater than the thickness of the cartridge100. The transmission suppression unit20has a light transmittance of 30% or less of the light generated from the measurement sample90in the thickness direction of the cartridge100(seeFIG.8). Note that the light transmittance in the thickness direction of the cartridge100is defined as the light transmittance of the portion of the cartridge100where the thickness is maximum. The light transmittance of light generated from the measurement sample90in the thickness direction of the cartridge100is preferably 15% or less. The light transmittance of light generated from the measurement sample90is more preferably 10% or less.

When a plurality of detection chambers10are provided along the surface of the flat plate-like cartridge100as described above, the transmission chamber20having at least the width of the thickness of the cartridge100is provided between the plurality of detection chambers10, such that it is possible to secure a sufficiently low light transmittance between the detection chambers10. Therefore, it is possible to effectively suppress the light generated in each of the plurality of detection chambers10from being mixed into another detection chamber10.

In the configuration example ofFIG.7, each of the plurality of detection chambers10is configured to store the measurement sample90even after detecting light generated from the measurement sample90. That is, the detection chamber10has no outlet for discharging the measurement sample90that has been subjected to the light detection. The cartridge100does not have a discharge passage for discharging the light-detected measurement sample90from the detection chamber10. Therefore, each of the plurality of detection chambers10continues to store the measurement sample90inside the detection chamber10even after the end of the light detection.

In this way the measurement sample90after the light detection is completed is kept stored inside the detection chamber10, and the emission of the measurement sample90that emits light to the outside of the detection chamber10can be avoided. Since the measurement sample90is not transferred to the outside of the detection chamber10, the light91generated from the measurement sample90can be reliably incident on the transmission suppression unit20. Therefore, for example, when light detection in each of the plurality of detection chambers10is performed sequentially, the light91generated from the moved measurement sample90due to the movement of the measurement sample90for which the light detection has been completed can be prevented from reaching another detection chamber10.

Processing Region

A specific configuration of the processing region60will be described. In the configuration example ofFIG.7, the three processing regions60have the same structure as each other. Therefore, only one processing region60will be described, and description of the remaining processing regions60will be omitted.

The processing region60includes a separation unit31and a recovery unit32, five processing chambers61to65, one detection chamber10, a passage40, six liquid storage units66, one liquid storage unit67, and an inlet30. A sample is injected into the inlet30. The sample is a blood sample of whole blood collected from a subject.

The passage40is provided separately for each of the plurality of detection chambers10and is fluidly connected to the detection chamber10. The passages40of one of the processing regions60are not fluidly connected to the passages40of the other processing region60. The passage40includes a plurality of passages41to45that fluidly connect each part in the processing region60.

The processing chambers61to65also are provided separately for each of the plurality of detection chambers10and are fluidly connected to the detection chamber10via the passage40. The processing chambers61to65of any one of the processing regions60are not fluidly connected to the processing chambers61to65of the other processing region60.

Each of the separation unit31, the recovery unit32, and the processing chambers61to65is a space that can accommodate a liquid. The separation unit31, the recovery unit32, and the processing chambers61to65are each partitioned by a wall51. The separation unit31, the recovery unit32, the processing chambers61to65, and the detection chamber10are arranged in the circumferential direction near the outer periphery of the main unit50.

The separation unit31is connected to the inlet30via the passage41. The sample injected from the inlet30is transferred to the separation unit31via the passage41by centrifugal force generated by rotation of the cartridge100.

The recovery unit32is disposed radially outward of the separation unit31and is connected to the separation unit31via the passage42. A sample flowing into the separation unit31from the passage41accumulates sequentially from the outside in the radial direction due to centrifugal force. When the sample stored in the separation unit31reaches the passage42, a larger amount of the sample is moved to the collection unit32by the action of the centrifugal force. In this way the amount of the sample stored in the separation unit31is determined to a fixed amount.

The sample processing performed in the processing region60includes a process of separating a liquid component and a solid component contained in the sample. The sample in the separation unit31is centrifuged into plasma as a liquid component and blood cells and other non-liquid components as a solid component by centrifugal force generated by rotation of the cartridge100. The plasma separated by the separation unit31moves to the passage43by capillary action. The passage43is narrowed at a connection immediately before the processing chamber61, and the plasma fills the passage43immediately before the processing chamber61.

The passage43is connected to the processing chamber61. When centrifugal force is applied by rotation of the cartridge100in a state in which the plasma fills the inside of the passage43, the plasma in the passage43is transferred to the processing chamber61. A predetermined amount of plasma to be transferred to the processing chamber61is determined by the volume of the passage43.

In the structural example ofFIG.7, the processing chambers61to65and the detection chamber10are arranged side by side in the circumferential direction so as to be adjacent to each other, and are connected via a passage45extending in the circumferential direction. As will be described later, between the processing chambers61to65and the detection chamber10, the test substance passes sequentially one by one through the passage45from one side (the processing chamber61side) to the other side (the detection chamber10side). The reagents stored in the corresponding liquid storage sections66are individually transferred to the processing chambers61to65and the detection chamber10via the passage44.

The liquid containing the test substance is transferred to the processing chamber61via the passage43. In the processing chamber61, magnetic particles MP are sealed. In the processing chamber61, the test substance contained in the sample is a complex with the magnetic particles MP. Therefore, after the processing chamber61, the test substance combined with the magnetic particles MP is transferred to another processing chamber via the passage40by a combination of the rotation of the cartridge100and the action of the magnetic force.

The passage45includes six radial regions45aextending in the radial direction and an arc-shaped circumferential region45bextending in the circumferential direction. The circumferential region45bis connected to the six radial regions45a. Five of the six radial regions45aare respectively connected to the corresponding five processing chambers61to65, and the other one radial region45ais connected to one detection chamber10. The six liquid storage units66are respectively connected to the passages45via the passages44in the radial direction. The six liquid storage units66are arranged radially alongside the corresponding processing chambers61to65and the detection chamber10. The liquid container67is connected to the passage44connecting the detection chamber10and the liquid container66mainly through a passage extending in the radial direction. A total of seven liquid storage units66and67are arranged on the inner peripheral side of the cartridge100, and the processing chambers61to65and the detection chamber10are arranged on the outer peripheral side of the cartridge100.

Each of the liquid storage units66and the liquid storage units67stores a reagent, and includes one sealing body68on the upper surface of both ends in the radial direction. The sealing body68can be opened by being pressed from above by the opening unit360(seeFIG.12) of the detection device300. The reagent in the liquid container66does not flow to the passage44before the sealing body68is opened, and the reagent in the liquid container66flows out to the passage44when the sealing member68is opened. When the cartridge100is rotated, the reagent moves to the corresponding processing chambers61to65and the detection chamber10by centrifugal force.

Note that each of the liquid storage units66and67invariably stores a reagent for a single measurement. That is, the cartridge100includes the liquid storage units66and67each storing a reagent that can perform one measurement of the test substance.

The measurement process includes a process of transferring a complex of the test substance and the magnetic particles MP from one of the processing chambers to another processing chamber or the detection chamber10. For example, the magnetic particles MP are moved in the radial direction by the magnetic force between the inside of the processing chamber61and the circumferential region45b. When the cartridge100is rotated, the magnetic particles MP move in the circumferential direction in the arc-shaped circumferential region45b. The magnetic particles MP carrying the test substance are sequentially moved to the processing chambers61to65and the detection chamber10by a combination of the radial movement due to the action of the magnetic force and the circumferential movement due to the rotation.

The measurement process includes a process of stirring the test substance and the reagent inside at least one of the processing chambers61to65and the detection chamber10by rotating the cartridge100. That is, the rotation speed of the cartridge100is changed, and acceleration and deceleration are alternately repeated. Due to the acceleration/deceleration, the liquid is moved back and forth in the circumferential direction in the chamber, and the complex is dispersed in the reagent.

In the cartridge100, after the test substance is carried on the magnetic particles MP in the processing chamber61, the test substance is mixed with the reagent in each of the processing chambers62,63,64, and65. The processing in the processing chambers61to65is set according to an assay for detecting a test substance. For example, the treatment with the reagent binds the test substance and a labeling substance. Finally, the magnetic particles MP carrying the test substance and the labeling substance are moved to the detection chamber10. In the detection chamber10, the preparation of the measurement sample90that emits light is completed. Light92(seeFIG.8) generated from the measurement sample90is detected by the photodetector331of the detection device300.

In the example ofFIG.7, three processing regions60are formed in one third of the main body50. However, the present invention is not limited to this configuration, inasmuch as two or four or more processing regions60also may be formed.

The number and shape of the processing chambers and passages also are not limited to those shown inFIG.7. The configuration of each part of the processing region60is determined according to the content of the sample processing assay performed in the processing region60.

The cartridge100contains reagent for a single use. In this case, the accuracy of the cartridge100cannot be controlled by measuring a control substance using the contained reagent. In order to perform quality control instead of measurement of the control substance, it is desirable to visually confirm from the outside that the processing has been properly performed in the cartridge100. Visual confirmation includes not only the case where the user visually recognizes the cartridge100but also the case where an image of the cartridge100is captured by the imaging unit and confirmed.

Therefore, in the configuration example ofFIG.7, the transmission suppression unit20is configured to transmit a part of the light traveling in the thickness direction of the cartridge100to the formation region of the passage40. Specifically, the transmission suppression unit20which forms the wall51does not completely block light incident in the thickness direction of the cartridge100in the region where the passage40is formed, but transmits the light at least partially. For example, as shown inFIG.9, the passage40is a through-hole (not shown) formed in the main body50or a non-penetrating recess, and is covered by the cover52. When the passage40is a through hole, similarly to the detection chamber10inFIG.8, the transmission suppression unit20does not cover the region where the passage40is formed in the thickness direction, and transmits light through the cover52. When the passage40is a non-penetrating recess as shown inFIG.9, it has a light transmittance that allows transmission. That is, the transmittance of the transmission suppression unit20in the thickness direction of the cartridge100is greater than 0%.

In this way the inside of the formation region of the passage40can be optically visually recognized or photographed even when the wall portion51is configured by the transmission suppression unit20. Therefore, it is possible to externally determine whether the transfer of the liquid such as the sample and the reagent in the passage40is appropriate. Accordingly, whether the detection processing of the test substance using the cartridge100has been appropriately performed is evaluated from the appearance, and the reliability of the detection accuracy of the test substance can be ensured insofar as the detection processing is appropriate. Therefore, the reliability of the detection accuracy of the test substance can be easily confirmed from the appearance of the cartridge100even when the wall51is formed by the transmission suppression unit20.

In the structural example ofFIG.7, the transmission suppression unit20is configured to transmit a part of the light traveling in the thickness direction of the cartridge100to the formation regions of the processing chambers61to65. Specifically, the transmission suppression unit20configuring the wall51does not completely block light incident in the thickness direction of the cartridge100in the region where the processing chambers61to65are formed, but transmits the light at least partially. For example, the processing chambers61to65are through holes or non-penetrating recesses formed in the main body50, and are covered by the cover52. When the processing chambers61to65are through holes, similarly to the detection chamber10ofFIG.8, the transmission suppression unit20does not cover the formation region of the processing chambers61to65in the thickness direction, such that light is transmitted through the cover52. When the processing chambers61to65are non-penetrating recesses, similarly to the passage40inFIG.9, the transmission suppression unit20can suppress the transmission of the light91between the detection chambers10and the processing chambers61to65, and the region where the processing chambers61to65are formed has a light transmittance such that light can be transmitted in the thickness direction.

In this way, similarly to the passage40, whether the processing of the test substance in the processing chambers61to65is appropriate can be grasped from the outside. Therefore, the reliability of the detection accuracy of the test substance can be easily confirmed from the appearance of the cartridge100even when the wall51is formed by the transmission suppression unit20.

Summary of Detection Device

Next, a specific configuration example of the detection device300that performs the detection method according to the present embodiment will be described.

The detection device300performs the measurement using the disk type cartridge100(seeFIG.7). The detection device300is a device that performs light detection by executing the above-described detection method (seeFIG.2). In the examples shown inFIGS.10to15, the detection device300is an immunoassay device that uses the cartridge100to detect a test substance in a sample using an antigen-antibody reaction, and measures the test substance based on the detection result.

In the structural examples ofFIGS.10and11, the detection device300includes a housing310that houses the photodetector331(seeFIG.12).

The housing310is configured by a box-shaped member having an internal space of a predetermined volume, a combination of a frame and an exterior plate, and the like. The housing310of the detection device300for PoC inspection has a small box-like shape that can be installed on a desktop.

The housing310includes a base311and a cover312. The cover312is provided so as to cover substantially the entire upper surface of the base311. An arrangement part313in which the cartridge100is arranged is provided on an upper surface portion of the base311. The cover312is provided to be openable and closable between a state in which the arrangement part313shown inFIG.10is opened, and a state in which the arrangement part313is covered as shown inFIG.11. The housing310is configured as a dark box configured to shield the cartridge100from the outside with the cover312covering the arrangement part313in which the cartridge100is arranged.

As shown inFIG.12, the detection device300includes a rotation mechanism320, a measurement unit330, and an imaging unit340. The detection device300also includes a magnet drive unit350, a plug opening unit360, a heater361and a temperature sensor362, and a clamper363. These components are housed in the housing310.

The arrangement part313(seeFIG.10) forms an upper surface of the base311which is openably and closably covered by the cover312. A support member314that supports the cartridge100from below is arranged in the arrangement part313. The support member314is formed of, for example, a turntable. The support member314is provided at the upper end of the rotation shaft321of the rotation mechanism320. The support member314is configured to support the cartridge100at a predetermined relative rotation angle.

The rotation mechanism320includes a rotation shaft321and a drive unit322such as a motor. The rotation mechanism320drives the drive unit322to rotate the cartridge100installed on the support member314about the rotation shaft321. The rotation mechanism320includes an encoder323for detecting the rotation angle of the drive unit322and an origin sensor324for detecting the origin position of the rotation angle. The cartridge100can be moved to an arbitrary rotation position by driving the drive unit322based on the detection angle of the encoder323with reference to the detection position of the origin sensor324.

The rotation mechanism320holds the cartridge100via the rotation shaft321. The rotation shaft321is arranged vertically, for example, when the detection device300is installed. The cartridge100is supported by the rotation mechanism320in a posture along the horizontal direction.

When the drive unit322rotates the rotation shaft321about the axis, the cartridge100rotates about the rotation shaft321. As a result, each part of the cartridge100, such as the detection chamber10, the processing chambers61to65, and the passage40, has a circular orbit having a rotation radius corresponding to a radial distance from the respective arrangement position to the rotation shaft321in the circumferential direction.

The rotation mechanism320is configured to execute at least a part of the measurement process by rotating the cartridge100about the rotation shaft321. The rotation mechanism320rotates the inside of the cartridge100by centrifugation of the blood sample, transfer of the sample, and transfer of the reagent to each of the processing chambers61to65and the detection chamber10(seeFIG.7), stirring of the reagent and the sample, transfer of the magnetic particles MP in the circumferential direction between the processing chambers61to65and the detection chamber10, and the like are performed as part of the measurement process.

The magnet drive unit350includes a magnet351and has a function of moving the magnetic particles MP inside the cartridge100in the radial direction. The magnet drive unit350is arranged below the arrangement part313, and is configured to move the magnet351in the radial direction. The magnet drive unit350is configured to move the magnet351in a direction approaching or retracting from the cartridge100. The magnetic particles MP in the cartridge100are collected by bringing the magnets351close to each other, and the magnetic collection of the magnetic particles MP is released by separating the magnets351.

The opening unit360projects a pin member360athat can advance and retreat toward the cartridge100from above the cartridge100arranged in the arrangement part313to make contact with the cartridge100to open the sealing body68(seeFIG.7) in the cartridge100via pressing. The two opening units360are provided so that the sealing body68provided at two locations for one liquid storage portion can be opened. After opening, the opening unit360moves the pin member360ato the retreat position where it is separated from the cartridge100and does not make contact.

The heater361is provided at a position directly below the cartridge100arranged in the arrangement part313and at a position immediately above the cartridge100, respectively. The heater361heats the sample contained in the cartridge100to a predetermined reaction temperature to promote the reaction between the sample and the reagent. The temperature sensor362detects the temperature of the cartridge100by infrared rays.

The measurement unit330includes a photodetector331at a position facing the cartridge100arranged on the arrangement part313via an opening formed in the base311. In this way the measurement unit330detects the light generated from inside the detection chamber10(seeFIG.13) by the photodetector331. The photodetector331detects the light92generated from the measurement sample90moved to the detection position332(seeFIG.14). The photodetector331outputs a pulse waveform corresponding to photons, that is, photons received. The measurement unit330includes a circuit therein, counts photons at regular intervals based on an output signal of the photodetector331, and outputs a count value.

The photodetector331is arranged at a position directly below the cartridge100arranged in the arrangement part313. As shown inFIG.14, the distance from the rotation axis321of the photodetector331substantially matches the distance from the rotation axis321of each detection chamber10in a plan view. The rotation mechanism320rotates the cartridge100about the rotation shaft321to arrange any one of the detection chambers10at the detection position332immediately above the photodetector331. As shown inFIG.13, the photodetector331detects light92generated from the measurement sample90and emitted in the second direction DR2for each of the plurality of detection chambers10. In the example ofFIG.13, the first direction DR1is a horizontal direction passing through the inside of the cartridge100, and the second direction DR2is a vertical direction orthogonal to the surface of the cartridge100.

As shown inFIG.13, the photodetector331is exposed through an opening on the upper surface of the base311that forms the inner surface315of the housing310. The photodetector331detects the light92in the second direction DR2emitted from the light extraction unit11of the detection chamber10arranged at the detection position332.

Here, the inner surface315of the housing310is formed of a material that absorbs light. The inner surface315of the housing310includes an upper surface of the base311and a lower surface of the cover312that form a light-shielding space that covers the arrangement part313. The light absorbing material is, for example, a black opaque material. The black opaque material is, for example, a resin material mixed with carbon black. Light generated from the measurement sample90in each of the detection chambers10is also radiated to the inside of the housing310via the light extraction unit11. The light94radiated inside the housing310is absorbed by the inner surface315of the housing310.

In the detection method performed by the detection device300described above, the scattering of light generated from the measurement sample90and emitted from the cartridge100to the outside of the cartridge100is suppressed by the inner surface315of the housing310that absorbs light generated from the measurement sample90. In this way the light94, among the light emitted from the measurement sample90emitted to the outside of the cartridge100and directed in a direction other than the second direction DR2enters the inner surface315of the housing310, is absorbed by the inner surface315of the housing310. As a result, it is possible to prevent the light94traveling in a direction other than the second direction DR2from being scattered in the housing310and mixed into another detection chamber10. That is, the light94is suppressed from being multiply reflected between the surface of the cartridge100and the inner surface315of the housing310and reaching the photodetector331, as shown inFIG.13.

A clamper363rotatably supports the center of the upper surface of the cartridge100installed on the support member314with the cover312closed. The cartridge100is supported while being sandwiched between the support member314and the damper363. The clamper363is configured to be able to stroke vertically in a predetermined range, and is forced toward the support member314side. The clamper363is provided with a stroke detection sensor (not shown), and is connected to a control unit370described later. It is possible to detect a state in which the cartridge100is not installed, a state in which the cartridge100is properly installed, and a state in which the cartridge100is installed improperly due to a displacement or the like.

The imaging unit340is provided so as to face the upper surface of the cartridge100installed on the support member314, and is configured to acquire an image of the cartridge100. It is possible to confirm whether the processing inside the cartridge100has been properly performed by the obtained image. The imaging unit340includes, for example, a CCD image sensor, a CMOS image sensor, and the like. The illumination unit341is configured by, for example, by a light emitting diode and generates illumination light at the time of imaging.

In the structural example ofFIG.12, the imaging unit340is fixed to the cover312. The imaging unit340directly faces the upper surface of the cartridge100via a hole provided in the cover312. The illumination unit341directly faces the upper surface of the cartridge100via a hole provided in the cover312. As shown inFIG.14, when the cartridge100arranged in the arrangement part313rotates, a part or all of the detection chamber10, the processing chambers61to65, the passage40and the like are set to pass the imaging range342of the imaging unit340. The rotation mechanism320arranges any of the detection chambers10, the processing chambers61to65, and the passage40within the imaging range342of the imaging unit340by rotating the cartridge100. The transmission suppression unit20transmits at least a part of the illumination light from the illumination unit341. Therefore, the imaging unit340acquires an image of the liquid or the magnetic particles MP inside the cartridge100using the illumination light.

The imaging unit340captures an image of an identifier (not shown) provided for each processing region60on the upper surface of the cartridge100. The identifier is an information recording medium that can be read from an image, such as a barcode or a two-dimensional code. The rotation mechanism320sequentially positions the identifiers within the imaging range342by rotating the cartridge100. Information for specifying the measurement item, information on the reagent, information for specifying the cartridge100, and the like are recorded in the identifier.

In addition, the detection device300shown inFIG.12includes an operation unit364that receives a user operation when opening the cover312, a detection unit365that detects opening and closing of the cover312, a locking mechanism366for locking the cover312in the closed state and the like.

FIG.15shows a control structure of the detection device300.

The detection device300includes a control unit370. Control unit370includes, for example, a processor and a memory. The processor includes, for example, a CPU, an MPU, and the like. The memory includes, for example, a ROM and a RAM. The control unit370receives a signal from each unit of the detection device300and controls each unit of the detection device300.

The detection device300includes a storage unit371. The storage unit371stores measurement result data. The storage unit371is configured by, for example, a flash memory, a hard disk, or the like.

The detection device300includes a communication unit372. The communication unit372is capable of transmitting information to an external device and receiving information from the external device. Communication unit372includes, for example, a communication module, an interface for external connection, and the like. The communication unit372can perform communication with a terminal (not shown) capable of communicating with the detection device300and communication with a server (not shown) via a network by wired or wireless communication. The communication enables transmission of a log including measurement result data and acquisition of data related to measurement processing such as a calibration curve. The terminals include, for example, tablet terminals, portable information terminals such as smartphones, and information terminals such as PCs (personal computers). The control unit370can receive a user's operation input via the user interface displayed on the terminal.

Description of Detection Device Operation

Next, the operation of the detection device300will be described with reference toFIG.16. The structure of the detection device300will be described with reference toFIG.12. The structure of the cartridge100will be described with reference toFIG.7andFIG.14.

First, as a preparation operation, the user injects a blood sample collected from a subject through the inlet30of the cartridge100. The user injects a sample to be measured into each of the three inlets30formed in the three processing regions60. As an example of the measurement items of the cartridge100, a measurement example of hepatitis B surface antigen (HBsAg) is shown. The test substance in the blood sample contains an antigen. The antigen is hepatitis B surface antigen (HBsAg). The measurement item also may be prostate specific antigen (PSA), thyroid stimulating hormone (TSH), thyroid hormone (FT4), or the like.

In the cartridge100, an R1 reagent is stored in a liquid storage unit66located in a radial direction of the processing chamber61. The processing chamber61contains an R2 reagent. An R3 reagent is stored in a liquid storage unit66located in the radial direction of the processing chamber62. A cleaning liquid is stored in each of the liquid storage units66located in the radial direction of the processing chambers63to65. An R4 reagent is stored in the liquid storage unit66located in the radial direction of the detection chamber10. The liquid storage unit67stores the R5 reagent.

In step S11ofFIG.16, the control unit370performs an initial operation for starting measurement.

Specifically, the control unit370detects the closure of the cover312after the user opens the cover312and installs the cartridge100on the support member314based on the signals of the detection unit365and the stroke detection sensor of the clamper363. The cartridge100is placed in the light-shielded housing310by closing the cover312. The control unit370causes an identifier (not shown) provided for each processing region60to be read. When the identifier is imaged by the imaging unit340, the control unit370acquires various information used for measurement. The control unit370also acquires the rotation position of each chamber and each sealing unit for each processing region60based on the origin position detected by the origin sensor324and the reading position of the identifier.

The control unit370causes the detection device300to start the processing of the sample and the light detection operation after step S12. At each step, the control unit370also positions each unit on which the sample processing has been executed in the imaging range342of the imaging unit340by the rotation mechanism320, and causes the imaging unit340to perform imaging. The control unit370monitors whether the sample processing has been normally executed based on the captured image of the imaging unit340. Note that if the execution has not been performed normally, the control unit370performs a predetermined error process, but that description is omitted here.

In step S12, the control unit370performs a process of transferring the sample to the separation unit31and a process of separating the sample into a liquid component and a solid component. The control unit370causes the rotation mechanism320to rotate the cartridge100at high speed, and moves the sample from the passage41to the separation unit31by centrifugal force. At this time, a surplus sample exceeding a predetermined amount moves to the collection unit32. In the separation unit31, the sample is separated into a liquid component as plasma and a solid component such as blood cells by centrifugal force. The separated plasma moves into the passage43and fills the passage43. By the rotation of the cartridge100, centrifugal separation is simultaneously performed in the three processing regions60.

In step S13, the control unit370transfers the plasma and the reagent to the processing chamber61. First, the control unit370performs positioning of the cartridge100by the rotation mechanism320and drives the opening unit360to open each of the sealing bodies68of the six liquid storage units66. When the opening of the first processing region60is completed, the control unit370executes the opening operation of the second processing region60and the third processing region60in order.

Next, the control unit370causes the rotation mechanism320to rotate the cartridge100. Due to the centrifugal force, the plasma is transferred from the passage43to the processing chamber61, and the reagents stored in the six liquid storage units66are transferred to the corresponding processing chambers61to65and the detection chamber10, respectively. The liquid is simultaneously transferred in the three processing regions60by the rotation of the cartridge100. In this way the plasma, the R1 reagent, and the R2 reagent are mixed in the processing chamber61. The R3 reagent is transferred to the processing chamber62. The cleaning liquid is transferred to the processing chambers63to65, respectively. The R4 reagent is transferred to the detection chamber10.

In step S13, when the transfer of the plasma and the reagent is completed, the control unit370also performs a stirring process for accelerating and decelerating the rotation of the cartridge100by the rotation mechanism320. In this way the liquid in the processing chambers61to65and the detection chamber10is stirred. Such a stirring process is performed not only in step S13but also in steps S14to S19after the transfer process. The stirring process is performed simultaneously in the three processing regions60by the acceleration and deceleration of the rotation of the cartridge100.

Here, the R1 reagent includes a capture substance that binds to the test substance. The capture substance includes, for example, an antibody that binds to the test substance. The antibody is, for example, a biotin-conjugated HBs monoclonal antibody. The R2 reagent contains magnetic particles MP. The magnetic particles MP are, for example, streptavidin-bound magnetic particles whose surface is coated with avidin. In step S13, when the plasma, the R1 reagent, and the R2 reagent are mixed and the stirring process is performed, the test substance and the R1 reagent bind by an antigen-antibody reaction. Then, the test substance bound to the capture substance of the R1 reagent binds to the magnetic particles MP via the capture substance by the reaction between the antigen-antibody reactant and the magnetic particles MP. As a result, a complex in which the test substance and the magnetic particles MP are bound is generated.

Next, in step S14, the control unit370transfers the complex in the processing chamber61from the processing chamber61to the processing chamber62in order for each processing region60.

When transferring the complex, the control unit370drives the magnet driving unit350to bring the magnet351closer to the cartridge100and collect the complex that spreads in the processing chamber61. The control unit370combines the radial movement of the magnet351by the driving of the magnet driving unit350and the circumferential movement of the cartridge100by the rotation mechanism320to move the complex along the passage45. That is, the control unit370moves the complex from inside the processing chamber61to the processing chamber62in the order of the radial inner movement of the path PT1, the circumferential movement of the path PT2, and the radial outer movement of the path PT3shown inFIG.14. When the transfer process in the first processing region60is completed, the control unit370sequentially performs the transfer processing on the second processing region60and the third processing region60. After moving the complex, the control unit370performs a stirring process. Note that the movement of the complex to each of the processing chambers63to65and the detection chamber10is performed by the same method, and thus a detailed description is omitted.

By transferring the complex to the processing chamber62, the complex generated in the processing chamber61and the R3 reagent are mixed in the processing chamber62. Here, the R3 reagent contains a labeling substance. The labeling substance includes a label, and a capture substance that specifically binds to the test substance. For example, the labeling substance is a labeled antibody using an antibody as a capture substance. In step S14, when the complex generated in the processing chamber61and the R3 reagent are mixed and agitated, the complex generated in the processing chamber61reacts with the labeled antibody contained in the R3 reagent. As a result, a complex in which the test substance, the capture antibody, the magnetic particles MP, and the labeled antibody are bound is generated in the processing chamber62.

In step S15, the control unit370transfers the complex in the processing chamber62from the processing chamber62to the processing chamber63in order for each processing region60. In this way in the processing chamber63, the complex generated in the processing chamber62and the cleaning liquid are mixed in the processing chamber63. In step S15, when the stirring process is performed, the complex and the unreacted substance are separated in the processing chamber63. That is, in the processing chamber63, unreacted substances are removed by cleaning.

In step S16, the control unit370transfers the complex in the processing chamber63from the processing chamber63to the processing chamber64in order for each processing region60. In this way the complex generated in the processing chamber62and the cleaning liquid are mixed in the processing chamber64. In the processing chamber64as well, unreacted substances are removed by cleaning.

In step S17, the control unit370transfers the complex in the processing chamber64from the processing chamber64to the processing chamber65in order for each processing region60. In this way the complex generated in the processing chamber62and the cleaning liquid are mixed in the processing chamber65. Unreacted substances also are removed by cleaning in the processing chamber65.

In step S18, the control unit370transfers the complex in the processing chamber65from the processing chamber65to the detection chamber10in order for each processing area60. In this way the complex generated in the processing chamber62and the R4 reagent are mixed in the detection chamber10. Here, the R4 reagent is a reagent for dispersing the complex generated in the processing chamber62. The R4 reagent is, for example, a buffer. In step S18, when the stirring process is performed, the complex generated in the processing chamber62is dispersed in the R4 reagent in the detection chamber10.

In step S19, the control unit370transfers the R5 reagent to the detection chamber10. Specifically, the control unit370causes the rotation mechanism320to position the cartridge100, and drives the opening unit360to open the sealing body68of the liquid storage unit67. The control unit370causes each of the three processing regions60to sequentially perform the opening operation. The control unit370rotates the cartridge100by the rotation mechanism320, and transfers the R5 reagent stored in the liquid storage unit67to the detection chamber10by centrifugal force. The R5 reagent is simultaneously transferred in the three processing areas60by the rotation of the cartridge100. In this way the R5 reagent is further mixed with the liquid mixture generated in step S18in the detection chamber10.

Here, the R5 reagent includes a luminescent substrate that generates light by reaction with the labeled antibody bound to the complex. In step S19, when the mixed solution generated in step S18and the additionally transferred R5 reagent are mixed and stirred, a measurement sample90(seeFIG.13) is prepared. The measurement sample90emits chemiluminescence when the labeling substance bound to the complex reacts with the luminescent substrate. As a result of step S19, the measurement sample90is disposed in each of the detection chambers10of the three processing regions60. As a result, light generated from the measurement sample90is emitted from each of the three detection chambers10.

In step S20, the control unit370causes the rotation mechanism320to position each of the detection chambers10at the detection position332immediately above the photodetector331. The photodetector331detects the light92emitted from the detection chamber10. The control unit370causes each of the plurality of detection chambers10to individually detect the light generated from the measurement sample90when the light generated from the measurement sample90is generated from each of the plurality of detection chambers10. That is, the control unit370causes the rotation mechanism320to position the first detection chamber10at the detection position332of the photodetector331, and to detect the light92generated from the measurement sample90. Next, the control unit370causes the rotation mechanism320to position the second detection chamber10at the detection position332of the photodetector331, and causes the light92generated from the measurement sample90to be detected. The control unit370causes the rotation mechanism320to position the third detection chamber10at the detection position332of the photodetector331, and causes the light92generated from the measurement sample90to be detected.

During a total of three light detections, the transmission of the light91generated from the measurement sample90radiated in the first direction DR1is suppressed by the transmission suppression unit20provided between each of the plurality of detection chambers10. For each of the plurality of detection chambers10, light92generated from the measurement sample90and emitted in the second direction DR2which is different from the first direction DR1is detected.

In step S21, the control unit370performs a measurement process regarding immunity based on the light detected by the photodetector331. The measurement unit330counts photons and outputs a count value. The control unit370measures the presence or absence and amount of the test substance based on the count value output from the measurement unit330and the calibration curve, and generates a measurement result.

When the measurement result is obtained, control unit370records the measurement result data in storage unit371in step S22. The control unit370also transmits measurement result data to a terminal or a server through communication unit372.

Thus, the measurement operation of the detection device300is completed.

In the above embodiment, chemiluminescence is light emitted by utilizing energy due to a chemical reaction, for example, light emitted when a molecule is excited by a chemical reaction to an excited state and then returns to the ground state. Chemiluminescence is generated, for example, by the reaction between an enzyme and a substrate, by applying an electrochemical stimulus to a labeling substance, by the LOCI (Luminescent Oxygen Channeling Immunoassay) method, or by generating bioluminescence. In the present embodiment, any chemiluminescence may be performed. A complex may be formed by combining a substance that is excited by fluorescence when irradiated with light of a predetermined wavelength and a test substance. In this case, a light source for irradiating the detection chamber10with light is arranged. The photodetector detects the fluorescence excited from the substance bound to the complex by the light from the light source.

Note that the magnetic particles MP may be any particles that include a material having magnetism used as a base material and are used in a normal immunoassay. For example, magnetic particles using Fe2O3 and/or Fe3O4, cobalt, nickel, phyllite, magnetite, or the like as a substrate can be used. The magnetic particles may be coated with a binding substance for binding to the test substance, or may be bound to the test substance via a capture substance for binding the magnetic particles to the test substance. The capture substance is, for example, an antigen or an antibody that binds to the magnetic particle and the test substance.

The capture substance is not particularly limited as long as it specifically binds to the test substance. For example, the capture substance binds to the test substance by an antigen-antibody reaction. More specifically, the capture substance is an antibody, but when the test substance is an antibody, the capture substance may be an antigen of the antibody. When the test substance is a nucleic acid, the capture substance may be a nucleic acid complementary to the test substance. Examples of the label contained in the labeling substance include an enzyme and a fluorescent substance. Examples of the enzyme include alkaline phosphatase (ALP), peroxidase, glucose oxidase, tyrosinase, and acid phosphatase. When performing electrochemiluminescence as chemiluminescence, the label is not particularly limited insofar as it is a substance that emits light by electrochemical stimulation, and examples thereof include a ruthenium complex. As the fluorescent substance, fluorescein isothiocyanate (FITC), green fluorescent protein (GFP), luciferin and the like can be used.

When the label is an enzyme, a known luminescent substrate may be appropriately selected as the luminescent substrate for the enzyme depending on the enzyme used. Examples of useful luminescent substrates when alkaline phosphatase is used as an enzyme include chemiluminescent substrates such as CDP-Star (registered trademark), (4-Chloro-3-(methoxyspiro [1,2-dioxetane-3,2′-(5′-chloro) triculo [3.3.13,7] decane]-4-yl) phenylphosphate disodium), CSPD (registered trademark) (3-(4-methoxyspiro [1,2-dioxetane-3,2-(5′-chloro) tricyclo [3.3.1.13,7] decane]-4-yl) phenyl disodium phosphate) and the like; luminescent substrates such as p-nitrophenyl phosphate, 5-bromo-4-chloro-3-indolyl phosphoric acid (BCIP), 4-nitro blue tetrazolium chloride (NBT), Iodonitrotetrazolium (INT) and the like; fluorescent substrates such as 4-methylum beryphenyl phosphate (4MUP) and the like; and chromogenic substrates such as 5-bromo-4-chloro-3-indolyl phosphoric acid (BCIP), disodium 5-bromo-6-chloro-indolyl phosphate, p-nitrophenyl phosphorus and the like.

Transmission Suppression Unit Modification

AlthoughFIG.7shows an example in which the transmission suppression unit20configures the wall51of the cartridge100wherein the entire wall51which forms the main body50is the transmission suppression unit20, only a part of the wall51may be configured by the transmission suppression unit20. The transmission suppression unit20need not necessarily configure the wall51, however. The transmission suppression unit20also may be a member different from the wall51.

For example, in the structural example ofFIG.17, the transmission suppression unit120is provided on a part of the wall51. That is, the transmission suppression unit120is configured by a member partially formed on the surface or inside the wall51with respect to the wall51that partitions the plurality of detection chambers10. In this way, for example, the transmission suppression unit120can be provided locally by forming a layer of the transmission suppression unit120on the surface of the wall51or embedding the transmission suppression unit120in a part of the wall51. In this way the transmission suppression unit120can be provided while securing a degree of freedom in selecting the constituent material of the wall51. For example, the transmission of light can be more effectively suppressed by the units20and120when a plurality of types of transmission suppression units are provided when the wall51is configured by the first transmission suppression unit20(seeFIG.8) and the second transmission suppression unit120is provided on the surface or inside of the wall51.

In the structural example ofFIG.17, the transmission suppression unit120is provided so as to divide the wall51. The transmission suppression unit120is provided continuously from the end54aon the rotation shaft321side of the cartridge100to the end54bon the side remote from the rotation shaft321. That is, the transmission suppression unit120extends in the radial direction of the cartridge100from the inner surface of the hole55which is the inner peripheral surface of the cartridge100to the outer peripheral surface of the cartridge100. A total of three transmission suppression units120are provided between the detection chambers10so as to partition between the three detection chambers10. In this way the light91in the first direction DR1bound between the detection chambers10always enters the transmission suppression unit120as indicated by the arrow inFIG.17. As a result, the transmission of the light91in the first direction DR1between the detection chambers10is suppressed by the transmission suppression unit120.

In the structural example ofFIG.17, the transmission suppression unit120extends linearly. The transmission suppression unit120may have a curved shape, a broken line shape, or a wide band shape. The transmission suppression unit120is formed to have a constant width. The width of the transmission suppression unit120also may change.

In the structural example ofFIG.17, the transmission suppression unit120includes the light scattering part22that scatters light generated from the measurement sample90. The light scattering part22includes a light scattering filler that scatters light generated from the measurement sample90. That is, the transmission suppression unit120is a resin mixed with a light scattering material. The resin is preferably a thermoplastic resin. The transmission suppression unit120may be, for example, a light-diffusing polypropylene resin, a light-diffusing acrylic resin, or the like.

In the structural example ofFIG.17, the wall51also may be translucent or may be transparent. As described above, the wall51may be configured by the transmission suppression unit20shown inFIG.17.

Although the transmission suppression unit120is provided continuously from the inner end54ato the outer end54bof the cartridge100in the structural example ofFIG.17, the transmission suppression unit120need not be continuous between both ends. For example, in the structural example ofFIG.18, the transmission suppression unit120does not reach the end54aor the end54bof the cartridge100. In the structural example ofFIG.18, the transmission suppression unit120has a continuous annular shape so as to surround the processing region60. The three transmission suppression units120are provided to circumscribe the three processing regions60that are fluidly isolated from each other. In this way the light91in the first direction DR1bound between the detection chambers10always enters the transmission suppression unit120as indicated by the arrow inFIG.18. As a result, the transmission of the light91in the first direction DR1between the detection chambers10is suppressed by the transmission suppression unit120.

Detection Chamber Modification

Although an example in which the three detection chambers10of the cartridge100are used for measuring the same measurement item has been described in the present embodiment, each of the plurality of detection chambers10may a different type of measurement item and type of sample to be used in optional combination.

In the example ofFIG.19, three detection chambers10are used for measuring different measurement items for the same sample. In the example ofFIG.19, the same sample A is injected into the inlet30of each processing region60. Then, different measurement items X, Y, and Z are measured for the measurement samples90accommodated in the respective detection chambers10. Each of the measurement items X, Y, and Z is, for example, any one of prostate specific antigen (PSA), thyroid stimulating hormone (TSH), and thyroid hormone (FT3, FT4).

In the example ofFIG.20, three detection chambers10are used for measurement of the same measurement item for different samples. In the example ofFIG.20, different samples A, B, and C are injected into the inlets30of the respective processing regions60. Then, the measurement of the same measurement item X is performed for the measurement samples90accommodated in the respective detection chambers10.

In the example ofFIG.21, the three detection chambers10are used for measurement of different measurement items for different samples. In the example ofFIG.21, different samples A, B, and C are injected into the inlets30of the respective processing regions60. Then, different measurement items X, Y, and Z are measured for the measurement samples90accommodated in the respective detection chambers10.

Note that the embodiments disclosed in this disclosure are illustrative in all aspects and not restrictive. The scope of the present invention is defined by the terms of the claims, rather than the description of the embodiments, and includes all modifications within the scope and meaning equivalent to the terms of the claims.