Automatic diagnostic analyzer for liquid samples
The analyzer's centralized tray design with dual reagent and reaction trays, robotic arm, and conveyor system addresses efficiency and space challenges, enabling simultaneous analysis processes and reducing operator workload.
Patent Information
- Application Number
- JP2022564619
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2020-04-30
- Filing Date
- 2021-04-12
- Publication Date
- 2025-06-25
- Estimated Expiration
- 2041-04-12
AI Technical Summary
Existing analyzers face challenges in efficiency, space utilization, and operator workload, necessitating improvements in automation and miniaturization while enabling multiple analysis processes.
The analyzer features a centralized sample tray surrounded by reagent and reaction trays, with dual dispensing devices and measuring devices, and incorporates a robotic arm for automated sample and reagent loading, along with a conveyor system for efficient operation and space optimization.
This configuration enhances efficiency, reduces operator burden, and allows simultaneous performance of multiple analysis processes like immunological and clinical chemical measurements, while minimizing device size and optimizing space usage.
Smart Images

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Abstract
Description
Technical Field
[0001] The present invention relates to an apparatus for the automatic analysis of liquid samples, comprising an analysis area having a sample tray for receiving sample containers, at least one reagent tray for receiving reagent containers, at least one reaction tray for receiving reaction containers, and at least one measuring device for measuring physical or chemical properties of a liquid sample processed with a reagent in a reaction container.
Background Art
[0002] As automation progresses in the field of medical and veterinary diagnosis, so-called analyzers, which are devices for automatically analyzing liquids, have come to be widely used. Such an analyzer automatically takes out a reagent from a reagent container, combines the reagent with a sample to be analyzed, and performs an analysis operation in a reaction container. Therefore, analyzers usually have a sample tray, a reagent tray, and a reaction tray, and are provided with slots for receiving and holding each container.
[0003] The process of taking out a reagent or a sample and transferring it into a reaction container is usually performed by an automatic dispensing device. Such an automatic dispensing device often includes a dispensing arm having a dispensing needle, and this dispensing arm is connected to a pump unit for sucking up a liquid into the dispensing needle and discharging the liquid from the dispensing needle again. The dispensing arm can move in the XY direction or rotate on a work area where a sample tray, a reagent tray, and / or a reaction tray are arranged.
[0004] Generally, an analyzer includes a measuring device for measuring physical or chemical parameters (process parameters) of a reaction mixture in a reaction container. The measuring device has measuring techniques such as spectrophotometry, colorimetry, ion-selective electrode method, coagulation method, immunoassay method, etc.
[0005] The area covered by the aforementioned device for performing diagnostic analysis is the analysis area, where a sample tray, at least one reagent tray, at least one reaction tray, a measurement device, and a pipetting device for transferring liquid between other devices are arranged.
[0006] An example of an analyzer is disclosed in International Publication WO2011 / 061118. To achieve maximum sample processing capacity, this analyzer has exactly three rotatable disks, namely a sample disk, a reagent disk, and a reaction disk, at least three dispensing devices, and a measurement device. To improve efficiency, this device is operated in continuous operating cycles each having a defined operating mode.
Summary of the Invention
Problems to be Solved by the Invention
[0007] Improving the efficiency of the automation of analyzers is always in demand. Also, for space saving in the laboratories where analyzers are installed, miniaturization of the devices is required. Further, it is also desirable to reduce the burden on the operators who operate the analyzers.
Means for Solving the Problems
[0008] According to the present invention, the above object is achieved by various aspects described in detail below. Usually, the device of the present invention commonly includes an analysis area, and the analysis area includes a sample tray for receiving a sample container containing at least one liquid sample, at least one reagent tray for receiving a reagent container containing at least one reagent, at least one reaction tray for receiving a reaction container, at least one measurement device for measuring physical or chemical properties of the liquid sample treated with the reagent in the reaction container, at least one dispensing device for transferring the liquid sample from the sample container in the sample disk to the reaction container, and at least one dispensing device for transferring the reagent from the reagent container in the reagent disk to the reaction container.
[0009] In connection with the present invention, the term "sample" is used to denote any material prepared for the purpose of an analytical operation and containing a substance to be diagnostically analyzed. Examples of samples include whole blood, serum, stored blood, etc., as well as body fluids such as urine and concentrated solutions.
[0010] The apparatus of the present invention is capable of performing different analytical processes. In a preferred embodiment, the physical or chemical property measured by at least one measuring device is selected from an immunoassay result, a clinical chemistry measurement result, a coagulation measurement result, or an ion-selective electrode measurement result in a reaction vessel.
[0011] First aspect: Arrangement of components
[0012] In order to enhance efficiency, minimize the size of the apparatus, and reduce the workload of the operator who operates the analyzer, the present invention provides many technical solutions.
[0013] According to a first aspect of the present invention, there is provided an automatic analyzer for liquid samples, comprising an analysis area, the analysis area including a sample tray for receiving sample containers, at least two reagent trays for receiving reagent containers, at least two reaction trays for receiving reaction containers, and at least two measuring devices for measuring physical or chemical properties, wherein the sample tray is disposed at the center of the analysis area, at least two reaction trays are disposed adjacent to the sample tray, at least two reagent trays are disposed adjacent to the reaction trays, at least two measuring devices are disposed adjacent to the reaction trays, and there is a dispensing device for transferring a liquid sample from a sample container in the sample tray to a reaction container in the reaction tray between the sample disk and each of the at least two reaction trays, and there is a dispensing device for transferring a reagent from a reagent container in the reagent tray to a reaction container in the reaction tray between each of the at least two reagent trays and the corresponding reaction tray.
[0014] According to a preferred embodiment, in the device of the present invention, the sample tray is in the form of a rotatable sample disk, at least two reagent trays are in the form of rotatable reagent disks, and at least two reaction trays are in the form of rotatable reaction disks arranged adjacent to the sample tray or in the form of static reaction rings. The dispensing device has a rotation axis at one end of a dispensing arm, and the other end of the dispensing arm is movable along a circular orbit around the rotation axis in the form of a pivoting dispensing arm. The rotation axis of the dispensing device is located between the sample disk and each reaction disk / ring, or between each reagent disk and its corresponding reaction disk / ring.
[0015] According to a first aspect of the present invention, the sample tray is preferably provided in the form of a rotatable sample disk arranged at the center of the analysis area. The "analysis area" is the area of the device of the present invention where the sample tray, reagent trays, reaction trays and dispensing device are located. In a preferred embodiment, the analysis area is planar and the devices are arranged in parallel. The "center" of the analysis area is defined by a quadrilateral, pentagon, hexagon or polygon formed by a virtual straight line connecting the rotation axes of the reagent trays and reaction trays. According to the present invention, the sample tray is arranged at the center of the analysis area when the rotation axis of the sample tray passes through the center of the analysis area defined by a quadrilateral, pentagon, hexagon or polygon formed by a virtual straight line connecting the rotation axes of the reagent trays and reaction trays.
[0016] In the present invention, the term "disk" refers to a circular tray that provides slots for receiving liquid containers such as sample containers, reagent containers, reaction containers, etc. In contrast, the term "ring" refers to a specific circular liquid container tray. In a perspective view of the circular tray from above, the ring body extends between two concentric circles, creating a central hole whose size is defined by the inner radius of the ring, where the inner radius of the ring is at least 30% of the outer radius of the ring.
[0017] In one embodiment, the sample tray is in the form of a sample disk having slots for receiving sample containers, and the slots are arranged in parallel along the outer peripheral edge of the disk. In an alternative embodiment, the sample tray is in the form of a sample disk having receiving pockets for receiving a long sample container rack, the rack having 2 to 20 slots for receiving sample containers, the slots being arranged in parallel along the central longitudinal axis of the rack, and the receiving pockets being radially oriented with respect to the sample disk.
[0018] The "dispensing device" according to the present invention has a dispensing needle connected to a pumping unit for sucking a liquid into the dispensing needle and discharging the liquid from the dispensing needle again. In a preferred embodiment of the present invention, the dispensing device comprises a pivoting dispensing arm. One end of the pivoting arm has a rotation axis, and the other end of the dispensing arm is movable along a circular orbit around it, thereby defining the working zone of the dispensing device. Thereby, the dispensing needle can be moved to a reagent container, a sample container and / or a reaction container.
[0019] Preferably, at least one rotation axis of the dispensing device is arranged between the sample disk and each reaction disk or reaction ring. Preferably, at least one rotation axis of the dispensing device is arranged between each reagent disk and the corresponding reaction disk or reaction ring.
[0020] Due to the arrangement of the components according to the specific embodiment of the present invention described above, it is possible to execute at least two different diagnostic analysis processes with the same analyzer. In particular, it is possible to combine immunological measurements and clinical chemical measurements within the same analyzer. Since there are at least two reagent trays for receiving the reagent containers required for each analysis procedure, it is possible to execute two different analysis processes. Furthermore, there are two independent reaction trays for each analysis procedure, and at least two measurement devices required for each procedure. Thus, all of these devices are provided at least in duplicate. However, there is only one sample tray arranged in the center of the analysis area. Therefore, it is possible to execute two different analysis processes on the sample provided in a single sample tray.
[0021] In a preferred embodiment of the present invention, the analysis area is arranged within the housing. In a more preferred embodiment, the housing of the device is provided with a loading port for receiving the sample container and the reagent container, either individually or pre-packed in a rack. Here, the loading port is provided with a robotic arm for transporting the sample container and the reagent container from the loading port to the sample tray and / or the reagent tray in the form of an individual or pre-packed rack.
[0022] The loading port including the robotic arm brings the beneficial effect that the operator of the analyzer does not need to manually load new samples and / or new reagents into the sample tray or reagent tray. Usually, when manually replacing samples and / or reagents, it is necessary to stop all moving operations in the analysis area to avoid contact with moving parts such as dispensing arms and / or rotating disks. Obviously, stopping all moving operations in the analysis area leads to delays in the process. Therefore, having a loading port equipped with a robotic arm for transporting sample containers and reagent containers to the sample tray and / or reagent tray is beneficial in that the movement of the robotic arm can be linked to any automated movement in the analysis area.
[0023] Furthermore, this robotic arm brings the beneficial effect that it can, if necessary, move liquid containers from a liquid container tray to other trays. For example, usually, calibration liquid or controls are placed in sample containers on the sample tray so that they are included in the analysis process. However, it is preferable to cool the calibration liquid / controls during the calibration process when the sample containers containing the calibration liquid or controls must be placed in the sample tray. For that purpose, the robotic arm can move the sample container containing the calibration liquid / controls from the sample tray, which is not usually cooled, to one of the reagent trays that are usually cooled.
[0024] In some embodiments, the device comprises an access control unit for linking the access of the robotic arm in the loading zone to the central sample tray with the access of the components arranged throughout for analysis to the central sample tray. In particular, the control unit determines the rules of access and the time slots allowed for various requesting units (robotic arm, analysis unit).
[0025] The control unit is connected to different components of the analyzer via signal transmission connections such as wired or Bluetooth. Through this connection, the robotic arm and the analysis unit (e.g., immunoassay unit, clinical chemistry unit) can communicate. In particular, through this connection, the robotic arm and the analysis unit can request time slots for accessing the central sample tray in order to place a sample container or a sample container rack on the sample tray, remove it from the same sample tray, or place a certain amount of sample on the sample container placed on the sample tray. Preferably, the request for a time slot is associated with a period attribute that defines a period when the time slot is requested. Even more preferably, the request for a time slot is associated with a priority attribute that indicates at least two priority levels (e.g., high / low), where a high priority level indicates that the allocation of a time slot within a given period is essential for proper operation, and a low priority level indicates that the allocation of a time slot within a given period is not essential for proper operation. Then, the control unit analyzes all requests optionally including period and / or priority level attributes and calculates an optimal working process to allocate a specific time slot for each access request. Finally, the relevant information regarding each time slot is communicated by the control unit to each of the requesting units.
[0026] In those embodiments, when there is a housing, the housing is formed by a floor, a ceiling, a rear wall, side walls, and a front wall. In a preferred embodiment, the loading opening is arranged on the front wall of the housing. Preferably, the loading opening is arranged in the middle of the left and right edges of the front wall.
[0027] In some embodiments, the loading port is designed to receive new sample containers and / or new reagent containers that are placed by hand by the operator of the analytical device or in the form of pre-packed racks on the loading port. Then, the robotic arm picks up the container / rack and transports it to the sample tray and / or reagent tray. Conversely, the empty container / rack is removed from the sample tray and / or reagent tray by the robotic arm and transported to the loading port where the operator can remove them. As a result, the "loading port" of the present invention is not only a "loading port" but also an "unloading port".
[0028] In a particular embodiment of the present invention, the device comprises a conveyor for transporting sample containers and / or reagent containers, either individually or in the form of pre-packed racks, to or from the loading port. The conveyor extends horizontally along the wall of the housing in which the loading port is located, from the loading port to the left and / or right side.
[0029] In the present application, the term "loading port" refers to the area of the wall of the device on which sample / reagent containers / racks are placed by the operator or conveyor so as to be picked up by the robotic arm. In contrast, the term "loading zone" refers to the area on the conveyor outside the loading port where the operator can place sample / reagent containers / racks.
[0030] In some embodiments, one end of the conveyor is outside the loading port, and the other end of the conveyor reaches into the loading port. At the one end outside the loading port, a plurality of sample containers and / or reagent containers can be placed on the conveyor individually or in the form of a pre-packed rack, and there is a loading zone where the conveyor transports the containers / racks one by one into the loading port. Further, such a conveyor enables used or empty sample containers and / or reagent containers taken out from a sample disk or a reagent disk and placed at the loading port by a robot arm to be transported to the outer end of the conveyor. In those cases, the conveyor is bidirectional, and the loading zone also serves as the unloading zone.
[0031] In other embodiments, one end of the conveyor is outside the left side of the loading port, and the other end of the conveyor reaches the loading port along the wall and extends to the right from the loading port. In those embodiments, the loading zone and the unloading zone of the conveyor are separated, i.e., there is a loading zone on one side from the loading port and an unloading zone on the other side.
[0032] In certain embodiments, two independent conveyors, one on the left and one on the right, are at the same horizontal level so as to face each other at the loading port. In other certain embodiments, at the same horizontal level, there are three independent conveyors: one starting from the left side of the loading port, one starting from the right side of the loading port, and one positioned inside the loading port.
[0033] In certain embodiments, there is at least one horizontal conveyor reaching the edge of the wall of the analyzer housing where the loading port is located, and the conveyor is for transporting liquid containers, individually or placed in a rack, to a second analyzer standing beside the edge of that wall of the analyzer housing. If the second analyzer is the analyzer according to the present invention including a conveyor reaching the loading port from the edge of the wall of the analyzer housing, the liquid containers can be transported from the first analyzer to the second analyzer for further analysis.
[0034] In certain embodiments, two or more of the analytical apparatuses of the present invention share one conveyor or a plurality of horizontally arranged conveyors for individually placing liquid containers or placing them in a rack and transferring them from one analytical apparatus to another.
[0035] The term "robot arm" refers to a movable conveying device having an end effector for conveying sample containers and / or reagent containers individually or in the form of a rack loaded with sample containers and / or reagent containers. In one embodiment, the robot arm has a swivel element through which a rotation axis passes at one end. Around the rotation axis, an end effector arranged at the other end of the swivel element with respect to the rotation axis can move along a circular orbit.
[0036] In a more preferred embodiment, the swivel arm can be moved along a vertical axis, and in a more preferred embodiment, the swivel element or the entire robot arm can be moved along a horizontal axis. In particular, it is preferred that the swivel element can be moved along a vertical axis and a horizontal axis.
[0037] All possible movements of movement around the rotation axis, movement along the vertical axis, and movement along the horizontal axis define the working zone of the robot arm, and in that working zone, the end effector can move to the sample containers and / or reagent containers in the loading port and also to the slots for receiving the sample containers or reagent containers of the sample tray and / or reagent tray. To minimize the required working zone, it is preferred to arrange the rotation axis between the sample disk and at least two reagent disks.
[0038] In certain embodiments, the robot arm comprises an end effector having at least two fingers movable relative to each other for gripping and conveying sample containers and reagent containers individually or in the form of pre-packed racks.
[0039] In certain embodiments of the present invention, the housing of the analyzer comprises a base and an openable hood, the analysis area is arranged on top of the base, and when the hood is closed, it completely covers the analysis area. In those embodiments, the loading port is preferably arranged on the base or the front wall of the hood, or extends across both the base and the front wall of the hood.
[0040] Regardless of which of the aforementioned alternative means is implemented, the loading port allows samples and / or reagents to be loaded into the analyzer without opening the hood. Furthermore, samples and / or reagents can be placed in the loading port at any time. There is no need to wait for a specific time slot to load samples and / or reagents into the analyzer. Whenever there is a time slot for loading a sample or reagent into the corresponding tray of the analyzer, the robotic arm can grip the sample or reagent from the loading zone and transport it to the corresponding tray.
[0041] To distinguish samples and different reagents, the sample containers and reagent containers can have labels with 1D codes (barcodes), 2D codes (matrix codes) or RFID (Radio-frequency identification). Accordingly, in a preferred embodiment, a 1D code reader, a 2D code reader and / or an RFID reader are provided in the loading zone to identify the samples and / or reagents placed by the operator in the loading zone. Before transporting the container to its destination location, the robotic arm moves the gripped container to the reader and, based on the information read from the code, the robotic arm performs the corresponding transport operation.
[0042] In a preferred embodiment, the control unit is connected to a 1D code reader, a 2D code reader, and / or an RFID reader in the loading zone via a signal transmission connection such as a wired connection or Bluetooth. Through this connection, the control unit can receive information about each container placed at the loading port. According to the information, the control unit can determine whether to place the container on the sample tray or the reagent tray. Then, the information about the designated position of the container is transmitted by the control unit to the robotic arm.
[0043] In some embodiments, each reagent container is individually placed within the loading port or on the conveyor. In other embodiments, the reagent containers are placed on a reagent container rack, and then the rack is placed within the loading port or on the conveyor. Alternatively, the robotic arm grips the reagent container while leaving the reagent rack on the conveyor, or the robotic arm grips the entire rack containing the reagent containers. The same alternative means also apply to gripping the sample container / sample container rack.
[0044] In some embodiments, the sample tray, the reagent tray, the reaction tray, and the loading port are elements surrounded by a single housing. However, in some embodiments, the housing is composed of physically separable units, one of which includes the sample tray and the loading port, and the other units respectively include a combination of the reagent tray, the reaction tray, and one measurement device.
[0045] The physically separable units have individual housings, and those housings are fixedly combined to form a compact analyzer, and a sample tray, at least two reagent trays, at least two reaction trays, and at least two measurement devices are arranged on the upper part of the compact analyzer. Preferably, a cover hood arranged via a hinge is provided on the upper part of the compact analyzer, and the cover hood covers the entire upper part of the analyzer, that is, all of the units.
[0046] In some specific embodiments, there is a combination of one immunoassay unit and one clinical chemistry unit. In other embodiments, two immunoassay units or two clinical chemistry units are combined. In some embodiments, 3, 4, 5, 6, 7, or 8 units are combined, and for each combination of two units, one loading zone used for the combination of the two units is provided.
[0047] In a preferred embodiment of the present invention, the device is arranged in the analyzer in accordance with at least one of the following symmetry rules. With respect to the side walls of the analyzer housing, the rotation axis of the sample disk is on the center line between the side walls, the center line of the loading port is on the center line between the side walls with respect to the side walls of the analyzer housing, the center position of the robot arm is on the center line of the loading port, the rotation axes of the first reagent disk on one side and the second reagent disk on the other side are at the same distance with respect to the center line between the side walls of the analyzer housing, the rotation axes of the first reaction disk or transfer ring on one side and the second reaction disk or transfer ring on the other side are at the same distance with respect to the center line between the side walls of the analyzer housing, the rotation axis of the first pivoting dispensing device between the first reagent disk on one side and the corresponding reaction disk / ring and the rotation axis of the second pivoting dispensing device between the second reagent disk on the other side and the corresponding reaction disk / ring are at the same distance with respect to the center line between the side walls of the analyzer housing, and the rotation axis of the first pivoting dispensing device between the sample tray on one side and the first reaction disk / ring and the rotation axis of the second pivoting dispensing device between the sample tray on the other side and the second reaction disk / ring are at the same distance with respect to the center line between the side walls of the analyzer housing.
[0048] By having a device arranged in the analyzer in accordance with one or more of the following symmetry rules, the exchange of the immunoassay unit and the clinical chemistry unit is facilitated.
[0049] When the sample tray is a sample disk, the diameter of the disk is in the range of 30 cm to 60 cm. When the reagent tray is a reagent disk, the diameter of the disk is in the range of 30 cm to 60 cm. When the reaction tray is a reaction disk / ring, the diameter of the disk is in the range of 30 cm to 60 cm.
[0050] To minimize the size of the analyzer of the present invention, the reaction tray is arranged adjacent to the central sample disk, and the reagent disk is arranged adjacent to the reaction tray. The term "adjacent" should be understood to define the shortest distance between the outer edges of two devices, and that distance is in the range of 5 cm to 15 cm, preferably in the range of 5 cm to 10 cm.
[0051] According to the present invention, the dispensing device is arranged between the sample tray and each reaction tray, or between each reagent tray and the corresponding reaction tray. The term "between" is understood to define that the working zone of the dispensing device located between two devices can move to the containers of both of the two devices.
[0052] In a preferred embodiment having a rotary dispensing device, the working zone of the rotary dispensing device has a radius in the range of 5 cm to 15 cm. Within this radius, for example, the dispensing needle of the dispensing device located between the sample disk and the reaction disk can be moved to both the sample container in the sample disk and the reaction container in the reaction disk.
[0053] Second aspect of the present invention: Static reaction ring
[0054] When performing an immunological measurement, it is necessary to culture the reaction mixture under defined conditions in order to ensure the time for reacting the target molecule and the antibody. The culture is particularly carried out under predetermined temperature conditions. Therefore, the reaction container containing the reaction mixture is usually placed in an adjusted incubator for a certain period of time.
[0055] According to one aspect of the present invention, there is provided an analyzer including an immunoassay unit and performing culturing in a reaction tray provided in the form of a static reaction ring. The static reaction ring has culture slots for receiving reaction vessels, and the slots are arranged in parallel in the circumferential direction of the ring. Outside the static reaction ring, a transport ring having at least one transport slot for receiving and transporting the reaction vessels is concentrically arranged, and the slots are arranged at the same height as the slots of the static reaction ring. The transport ring has at least one pusher for reciprocally transferring the reaction vessel from at least one transport slot of the transport ring to one of the culture slots of the static reaction ring by horizontal movement on the radial axis of the reaction ring.
[0056] According to a preferred embodiment of the present invention, the slots of the static reaction ring are made of metal. Preferably, the static reaction ring is an integral type made of metal having slots for receiving reaction vessels as an integral part.
[0057] In a specific embodiment of the present invention, the static reaction ring has a single row of slots arranged in parallel in the circumferential direction on the outer peripheral edge of the ring. In an alternative embodiment, the static reaction ring has a first row of slots arranged in parallel in the circumferential direction on the outer peripheral edge of the ring and a second row of slots arranged in parallel in the circumferential direction in the direction towards the central axis of the ring.
[0058] To adjust the static reaction ring, a heating device for heating a metal slot or an integral metal ring including the slot as an integral part is provided. The heating device has means for controlling and maintaining the temperature of the static reaction ring within a range from 20°C to 50°C.
[0059] In some embodiments, the reaction vessel is a cuvette having a base area with a long side and a short side, and each long side of the cuvette is oriented along the radial axis of the reaction disk. Accordingly, the slots of the static reaction ring have their long sides oriented along the radial axis of the static reaction ring.
[0060] The transfer ring is rotatably arranged around the static reaction ring. The transfer ring has one, two, three or four slots for receiving reaction vessels. The transfer ring has a pusher arranged one by one in each slot, for reciprocally transferring the reaction vessel from the corresponding slot of the transfer ring to one of the slots of the static reaction ring by horizontal movement on the radial axis of the reaction ring.
[0061] In some specific embodiments of the present invention, there is at least one external slot outside the transfer ring in the radial direction for receiving a reaction vessel. The external slot is at the same height as the transfer slot for receiving and transferring the reaction vessel in the transfer ring, so that the reaction vessel can be reciprocally transferred from the slot of the transfer ring to the external slot by horizontal movement on the radial axis of the transfer ring. In those embodiments, the transfer ring has at least one pusher for reciprocally transferring the reaction vessel from at least one transfer slot of the transfer ring to one of the external slots by horizontal movement on the radial axis of the reaction ring.
[0062] The aforementioned external slot is provided as a parking position for further processing of the reaction mixture in the reaction vessel, such as bead separation, aggregation analysis, mixing, and cleaning of the reaction vessel.
[0063] To maintain the temperature inside the circular static reaction ring and avoid warming the reaction mixture in the reaction vessel arranged in one of the external slots by the heated reaction ring, a circular thermal separation housing is provided around the reaction ring. The cross-section of the circular separation housing has an upside-down "U" shape.
[0064] The third aspect of the present invention: Circular measurement chamber
[0065] According to a third aspect of the present invention, there is provided an analytical apparatus having at least one measuring device, wherein the at least one measuring device measures the optical properties of a liquid sample treated with a reagent in a reaction vessel. The measuring device has a cylindrical wall and a cylindrical top, and has a rotatable transport cylinder with at least one slot in the cylindrical wall for receiving the reaction vessel. It has a cylindrical housing having a cylindrical wall and a cylindrical top, and being arranged concentrically around the transport cylinder, the cylindrical housing having at least one slot for inserting the reaction vessel into and / or discharging it from at least one slot of the transport cylinder, and has a photodetector for detecting light emitted from the liquid in the reaction vessel inserted into at least one slot of the transport cylinder.
[0066] By rotation of the transport cylinder, at least one slot for receiving the reaction vessel can be moved from a loading position to a detection position and further to a discharge position. In some embodiments, at least one treatment position is provided where a reagent is added to the reaction mixture, and in the moving direction, such a treatment position is between the loading position and the detection position.
[0067] The cylindrical housing and the transport cylinder are designed to provide a loading opening for loading the reaction vessel into at least one slot when the transport cylinder is in a loading position with respect to at least one slot. The cylindrical housing and the transport cylinder are designed to provide a discharge opening for discharging the reaction vessel from at least one slot when the transport cylinder is in a discharge position with respect to at least one slot. Further, the cylindrical housing and the transport cylinder are designed such that when at least one slot is in a light detection position, the transport cylinder holds the reaction vessel in the at least one slot in a position immediately in front of a light opening provided in the cylindrical wall of the cylindrical housing, so that light emitted from the liquid in the reaction vessel passes through the light opening and reaches a photodetector arranged on the other side of the light opening.
[0068] The circular measurement chamber of the present invention is designed to measure the optical properties of a liquid sample, particularly when the light intensity of the object to be detected is low or when accurate quantification is required. An example of an analysis where the light intensity of the object to be detected is quite low and accurate quantification is necessary is CLIA (chemiluminescence immunoassay). In such cases, it is necessary to avoid external photons reaching the detector by performing the measurement in complete darkness.
[0069] As a highly sensitive photodetector required in such cases, a PMT detector having a photomultiplier tube can be exemplified.
[0070] By precisely fitting the rotatable transport cylinder within the cylindrical housing, a very small gap is obtained that minimizes backlash when the transport cylinder is rotated within the housing. In some embodiments, the maximum distance between the outer periphery of the transport cylinder wall and the inner periphery of the cylindrical housing wall is 1 mm or less. This is to ensure a light-shielding arrangement so that light potentially incident at the loading position when loading the reaction vessel into the transport cylinder does not reach the photodetector at the detection position.
[0071] The number of slots in the transport cylinder wall is preferably one, two, or three. In those embodiments, when there are two slots in the transport cylinder, the two slots are arranged at opposing positions on the outer peripheral edge of the transport cylinder, i.e., at an angle of 180° with respect to each other. In those embodiments, when the rotatable transport cylinder has three slots for receiving the reaction vessel, the slots are preferably arranged in the cylinder wall at an angle of 120° with respect to each adjacent slot on the outer peripheral edge of the transport cylinder.
[0072] By orienting the slots as described above, the risk of photons reaching from the loading position to the detection position is minimized. Furthermore, the risk of photons reaching from the loading opening to the detection opening is minimized in a preferred embodiment of the present invention where vertical fins project upward or downward from the horizontal surfaces of the transport cylinder and / or the cylindrical housing.
[0073] In some embodiments, some vertical fins extend linearly and parallel to each other from one edge of the corresponding surface to the opposite edge of that surface. In certain embodiments, a first set of vertical fins extend linearly and parallel to each other from one edge of each surface to the opposite edge of that surface, and a second set of fins also extend linearly and parallel to each other from one edge of each surface to the opposite edge of that surface, intersecting the first set of fins at an angle within the range of 30° to 90°.
[0074] In other specific embodiments, the vertical fins are arranged concentrically. In particularly specific embodiments, the vertical fins are arranged concentrically and protrude upward from the outer surface of the top of the conveying cylinder and / or protrude downward from the inner surface of the top of the cylindrical housing, and the fins are arranged concentrically around the axis of rotation of the conveying cylinder.
[0075] In some embodiments, the cross-section of the fin is rectangular, triangular, semi-circular or a combination thereof. In certain embodiments, when there are fins on opposing surfaces, such as both the outer surface of the top of the conveying cylinder and the inner surface of the cylindrical housing, the fins may be designed to match, and adjacent fins may have their vertices aligned or engaged with each other such that the vertex of a fin on one surface reaches the gap between the fins on the other surface and vice versa.
[0076] Further embodiments are characterized in that the cylindrical housing has one loading port for inserting the reaction vessel into the slot of the conveying cylinder and one outlet port for discharging the reaction vessel from at least one slot of the conveying cylinder, the loading port being at the cylinder top of the cylindrical housing and the outlet port being at the cylinder wall of the cylindrical housing.
[0077] Any features that can be gathered by those skilled in the art from this specification, the drawings, and the claims may be combined individually, in the same way as any other combination of the features or groups of features disclosed herein, unless they are explicitly excluded or the technical conditions render such a combination impossible or meaningless, even if they are only described in the context of a particular additional feature. Note that an exhaustive and explicit discussion of possible combinations of features has been omitted for the sake of brevity and readability of the specification and the claims.
[0078] In particular, note that those features described in the context of one of the above-described aspects of the present invention may be combined with the features described in the context of another of the above-described aspects of the present invention.
[0079] Also, it is obvious to those skilled in the art that the attached drawings and the following specific description, which are described as exemplary embodiments, exemplarily present possible configurations of the present invention. Therefore, those skilled in the art will easily understand that all other structures having the features or combinations of features according to the present invention as described in the claims are also within the protection scope of the present invention. An exhaustive and clear presentation of all possible embodiments has been omitted simply for the sake of brevity and readability of this specification.
Brief Description of the Drawings
[0080] [Fig. 1] Fig. 1 is a perspective view of the upper surface of an analyzer according to an embodiment of the present invention as seen from above. [Fig. 2] Fig. 2 is a detailed view of a static reaction ring of an analyzer according to an embodiment of the present invention. [Fig. 3] Fig. 3 is a perspective view of a circular measurement chamber of an analyzer according to an embodiment of the present invention. [Fig. 4] Fig. 4 is an explanatory view showing another embodiment of the circular measurement chamber shown in Fig. 3 in an analyzer according to an embodiment of the present invention.
Embodiments for Carrying Out the Invention
[0081] FIG. 1 is a perspective view of the upper surface of the analyzer 1 according to an embodiment of the present invention as viewed from above. In the analysis area 2 of this analyzer 1, two reagent trays 5 and 6 are arranged, and both of these reagent trays 5 and 6 are in the form of rotatable disks. Further, in the analysis area 2, two reaction trays 9 and 10 are arranged. One reaction tray 9 is in the form of a rotatable reaction disk, and the other reaction tray 10 is in the form of a static reaction ring 10.
[0082] A rectangle formed by a dashed line connecting the rotation axes of the reagent trays 5 and 6 and the rotation axes of the reaction trays 9 and 10 defines the center of the analysis area 2. The rotation axis of the sample tray 3 passes through the center of the analysis area 2. Thus, the sample tray 3 is arranged at the center of the analysis area 2.
[0083] The two reagent trays 5 and 6 are adjacent to the sample tray 3, on the right side and the left side of the sample tray 3 respectively. Further, the two reaction trays 9 and 10 are adjacent to the sample tray 3, with one provided on the right side and one provided on the left side.
[0084] Between the sample tray 3 and each of the two reaction trays 9 and 10, there are dispensing devices 15 and 16. Further, between the reaction tray 9 and the reagent tray 5, there are two dispensing devices 17, and between the reaction tray 10 and the reagent tray 6, there is one dispensing device 18. The dispensing devices 15 and 16 between the sample tray 3 and the reaction trays 9 and 10 are for transferring a liquid sample from the sample container 4 in the sample tray 3 to the reaction containers 11 and 12 in the reaction trays 9 and 10. The dispensing devices 17 and 18 between the reagent trays 5 and 6 and the reaction trays 9 and 10 are for transferring reagents from the reagent containers 7 and 8 in the reagent trays 5 and 6 to the reaction containers 11 and 12 and the reaction trays 9 and 10.
[0085] The dispensing devices 15, 16, 17, 18 are in the form of a swing-type dispensing arm having a rotating shaft 19 at one end of the dispensing arm, and a dispensing needle 20 at the other end thereof is movable along a circular orbit around the rotating shaft 19. The rotating shafts 19 of the dispensing devices 15, 16, 17, 18 are disposed between the sample disk 3 and each of the reaction trays 9, 10, or between each of the reagent trays 5, 6 and the corresponding reaction trays 9, 10.
[0086] Measurement devices 13, 14 are provided adjacent to each of the reaction trays 9, 10. The measurement device 14 adjacent to the reaction tray 10 is a PMT detector having a photomultiplier tube for measuring chemiluminescence in immunoassay. The measurement device 13 adjacent to the reaction tray 9 is a photometer for measuring the optical characteristics of a clinical chemistry reaction mixture. The sample tray 3 has receiving pockets 28 for receiving long sample container racks 24. Each container rack has five slots for receiving sample containers 4, and the five slots are arranged in parallel along the longitudinal axis of the rack. The receiving pockets 28 are radially oriented on the sample tray 3. In this embodiment, there are ten receiving pockets 28. Therefore, when fully filled, the sample tray 3 of this embodiment can carry ten sample container racks each having five slots. As a result, the sample tray 3 can carry a maximum of fifty sample containers in total.
[0087] The reagent tray 6 has fourteen receiving pockets for receiving reagent container racks, and each of the racks has three slots for receiving reagent containers 8. The reagent container racks are radially oriented on the outer peripheral side of the disk of the reagent tray 6.
[0088] The disk of the reagent tray 5 has 24 pockets for receiving the reagent container racks 23, and each of the reagent container racks has two slots for receiving the reagent containers 7. The pockets for receiving the reagent container racks are arranged in two rows, one row on the outer peripheral side of the disk of the reagent tray 5 and one row on the central side of the disk of the reagent tray 5.
[0089] The reaction tray 9 has approximately 100 slots for receiving the reaction vessels 11 on the outer peripheral side of its disk. In this embodiment, the reaction vessel is a cuvette for the photometric analysis of the reaction mixture contained therein. By rotating the disk of the reaction tray 9, each reaction vessel 11 can be transported to the photometer 13 for measuring the optical properties of the reaction mixture contained therein.
[0090] The reaction tray 10 is a static reaction ring, and a transfer ring 30 for transporting the reaction vessel 12 to and from the static reaction ring 10 is concentrically arranged outside the static reaction ring.
[0091] According to FIG. 1, the illustrated embodiment of the analyzer 1 has an analysis area arranged in a plane inside the housing 21, where the housing 21 has a loading port 22 on its front wall 26. The loading port 22 is for receiving the sample container 4 and the reagent containers 7, 8 individually or in a state pre-packed in the racks 23, 24. The loading port 22 is provided with a robot arm 25 for transporting the sample container 4 and the reagent containers 7, 8 from the loading port 22 to the sample tray 3 or the reagent trays 5, 6 individually or in the form of the pre-packed racks 23, 24. Further, the robot arm 25 can transport the sample container from the sample tray 3 to the reagent trays 5, 6 or vice versa. In those embodiments, when the reagent trays 5, 6 are cooled, the sample rack 24 carrying the filled sample container can also be moved to the cooling reagent trays 5, 6 to extend the life of the control.
[0092] In the illustrated embodiment, the robotic arm 25 is a rotatable arm having a rotation axis at one end of the arm, and the other end thereof is movable along a circular path around the rotation axis. At the end of the arm opposite to the rotation axis, the robotic arm has an end effector for gripping and transporting sample containers and reagent containers individually or in the form of pre-packed racks.
[0093] The robotic arm can move along a horizontal axis from the left side (where the reagent tray 6 is located) to the right side (where the reaction tray 5 is located) in order to place the reagent container / rack or reagent trays 5, 6 or to pick them up from the reagent tray 5 or 6. Further, the robotic arm 25 can pick up the container / rack from the height of the loading port 22 which is lower than the height of the analysis area 2, transport them to the height of the analysis area, and move them along a vertical axis in order to place them, for example, in the reagent trays 5 or 6.
[0094] In addition to the circular movement of the swivel arm, due to the mobility along the horizontal axis and the vertical axis, the robotic arm 25 can move the end effector within the working zone, within which the end effector can grip the sample container and / or reagent container individually or in the form of a pre-packed rack from the loading port 22, reagent trays 5, 6 and / or sample tray 3, transport them from or to one of those devices, and / or place them into one of those devices.
[0095] On the front wall 26 of the housing 21, there is provided a horizontal recess for providing a conveyor 27 that reaches from the left side to the right side through the loading port 22. When the container / rack loaded in the sample tray 3 and / or the reagent trays 5, 6 is placed on the conveyor 27, the conveyor 27 transports the container / rack to the loading port 22, where the robotic arm 25 picks up the container / rack and transports them into the analysis area.
[0096] Figure 2 shows details of the static reaction ring 10 of a particular embodiment of the analyzer 1 of the present invention. The static reaction ring 10 has slots 29 for receiving the reaction vessel 12, and the slots 29 are arranged in parallel circumferentially on the static reaction ring 10. Outside the static reaction ring 10, a transport ring 30 having one slot 31 for receiving the reaction vessel 12 is arranged concentrically, and the slot 31 is arranged at the same height as the slot 29 of the static reaction ring 10. For this reason, the pusher 32 arranged on the transport ring 30 can transfer the reaction vessel 12 from the transport ring slot 31 to one of the slots 29 of the static reaction ring 10 by horizontal movement on the radial axis of the static reaction ring 10. Also, the same pusher 32 can take out the reaction vessels 12 from the slots 29 of the static reaction ring and transfer them to the transport slot 31 and the transport ring 30.
[0097] In the particular embodiment of FIG. 2, an external slot 46 is provided outside the transport ring. The external slot 46 is for receiving the reaction vessel, and the reaction vessel 12 can be placed in the external slot 46 by the pusher 32 by horizontal movement directly from the transport ring 13 or by horizontal movement from the static reaction ring 10 through the transport ring 30 to the external slot 46.
[0098] In the embodiment of FIG. 2, the external slot 46 is a parking position for further processing of the reaction mixture inside the reaction vessel 12 arranged in that parking position. The further processing may be, for example, a mixing step, a magnetic bead separation step or any other further processing step.
[0099] In the particular embodiment shown, the static reaction ring 10 has a single row of slots 29 arranged in parallel circumferentially on the outer peripheral edge of the ring.
[0100] Figures 3 and 4 show a circular measurement chamber according to a particular embodiment of the analyzer of the present invention. Figure 3 is a perspective view of the circular measurement chamber, particularly including a cylindrical housing 37, and Figure 4 is a perspective view of the same measurement chamber without the cylindrical housing 37.
[0101] The measuring device 14 shown in Figures 3 and 4 is for measuring the optical properties of a liquid sample treated with a reagent in the reaction vessel 12. The measuring device 14 comprises a rotatable transport cylinder 33 surrounded by a cylindrical housing 37. On one side of the measuring device 14, there is provided a photodetector 41 for detecting light emitted from the liquid in the reaction vessel 12 inserted into one of the slots 36 of the transport cylinder 33.
[0102] The rotatable transport cylinder 33 has a cylinder wall 34 and a cylinder top 35, and the cylinder wall 34 is provided with three slots 36 for receiving the reaction vessel 12. In the illustrated embodiment, the three slots 36 for receiving the reaction vessel 12 are arranged in the cylinder wall at an angle of 120°.
[0103] The transport cylinder 33 is rotatable and surrounded by a cylindrical housing 37. The cylindrical housing 37 has a cylindrical housing wall 38 and a cylindrical housing top 39, and the cylindrical housing 37 is arranged concentrically around the transport cylinder 33 and is provided with one opening 43 for inserting the reaction vessel 12 into the slot 36 of the transport cylinder 33 and one opening 44 for discharging the reaction vessel 12 from the slot 36 of the transport cylinder 33.
[0104] In the embodiment shown in Figures 3 and 4, vertical fins 42 protruding upward from the transport cylinder top 35 are provided. The vertical fins 42 are arranged concentrically on a circumference centered on the rotation axis of the transport cylinder 33. Further, the fins 42 have a triangular cross-section and the cylindrical housing TopIt is adapted to match adjacent fins arranged on the opposing surface of 39. In particular, the adjacent fins engage with each other such that the apex of the fin on one surface reaches within the gap between the fins on the other surface, and vice versa.
Explanation of Signs
[0105] 1 Automatic analyzer for liquid samples (Analyzer) 2 Analysis area 3 Sample tray 4 Sample container 5 First reagent disk 6 Second reagent disk 7 First reagent container 8 Second reagent container 9 Reaction disk 10 Reaction ring 11 First reaction container 12 Second reaction container 13 First measurement device 14 Second measurement device 15 First dispensing device 16 Second dispensing device 17 First dispensing device 18 Second dispensing device 19 Rotation axis 20 Dispensing needle 21 Housing 22 Loading port 23 Reagent rack 24 Sample rack 25 Robot arm 26 Front wall 27 Conveyor 28 Pocket for receiving sample rack 29 Slot for receiving reaction container 30 Conveyor ring 31 Slot for receiving reaction container 32 Pusher 33 Conveyor cylinder 34 Cylinder wall 35 Cylinder top Slot for receiving a reaction vessel in the 36-cylinder wall 37 Cylindrical housing 38 Cylindrical housing wall 39 Cylindrical housing top 41 Photodetector 42 Vertical fin 43 Loading port for inserting the reaction vessel 44 Outlet for discharging the reaction vessel 45 Side wall 46 External slot for receiving the reaction vessel
Claims
1. An apparatus (1) for the automatic analysis of liquid samples, said apparatus comprising an analysis area (2), wherein said analysis area includes a sample tray (3) for receiving a sample container (4), at least two reagent trays (5, 6) for receiving reagent containers (7, 8), at least two reaction trays (9, 10) for receiving reaction containers (11, 12), and at least two measuring devices (13, 14) for measuring physical or chemical properties, wherein said sample tray (3) is a sample disk arranged at the center of said analysis area (2), wherein said at least two reaction trays (9, 10) are arranged adjacent to said sample tray (3), wherein said at least two reagent trays (5, 6) are arranged adjacent to said reaction trays (9, 10), wherein said at least two measuring devices (13, 14) are arranged adjacent to said reaction trays (9, 10), wherein between each of said sample disk (3) and said at least two reaction trays (9, 10), dispensing devices (15, 16) are provided for transferring a liquid sample from the sample container (4) in said sample tray (3) to the reaction container (11, 12) in said reaction trays (9, 10), and between each of said at least two reagent trays (5, 6) and the corresponding reaction tray (9, 10), dispensing devices (17, 18) are provided for transferring a reagent from the reagent container (7, 8) in said reagent tray (5, 6) to the reaction container (11, 12) in said reaction trays (9, 10), and said analysis area is arranged within a housing (21), said housing having a loading opening (22) for receiving the sample container (4) and the reagent containers (7, 8) either individually or in a pre-packed state in racks (23, 24), said loading opening (22) comprising one robot arm (25) for transporting the sample container (4) and the reagent containers (7, 8) either individually or in the form of a pre-packed rack (23, 24) from said loading opening (22) to said sample tray (3) or said reagent trays (5, 6).
2. wherein said sample tray is in the form of a rotatable sample disk (3), wherein said at least two reagent trays are in the form of rotatable reagent disks (5, 6), The at least two reaction trays are in the form of a rotatable reaction disk (9) arranged adjacent to the sample tray or in the form of a static reaction ring (10), The dispensing device is in the form of a pivoting dispensing arm (15, 16, 17, 18) having a rotation axis (19) at one end of the dispensing arm and around which a dispensing needle (20) at the other end of the dispensing arm is movable along a circular orbit, and the rotation axis of the dispensing device is disposed between the sample disk (3) and each reaction disk / ring (9, 10), or between each reagent disk (5, 6) and the corresponding reaction disk / ring (9, 10). The apparatus according to claim 1, characterized in that it is arranged.
3. The apparatus according to any one of claims 1 or 2, characterized in that the loading port is arranged on the front wall (26) of the housing (21).
4. The apparatus according to any one of claims 1 to 3, characterized in that the loading port is provided with a reader for 1D code, 2D code and / or RFID.
5. The apparatus according to any one of claims 1 to 4, characterized in that it comprises a conveyor (27) for transporting the sample container and / or the reagent container, either individually or in the form of a pre-packed rack, to or from the loading port.
6. The physical or chemical property measured by at least one of the at least two measuring devices is the result of an immunoassay, or the result of a clinical chemistry measurement, or the result of an agglutination measurement, or the result of an ion-selective electrode measurement. The apparatus according to any one of claims 1 to 5, characterized in that it is.
7. The sample disk (3) has a receiving pocket (28) for receiving a long sample container rack (24) having 2 to 20 slots for receiving sample containers (4) along the central longitudinal axis of the rack, and the receiving pocket (28) is radially oriented on the sample disk (3). The apparatus according to any one of claims 1 to 6, characterized in that it is.
8. At least one of the reaction trays is in the form of a static reaction ring (10) having a slot (29) for receiving the reaction vessel (12), the slots (29) being arranged in parallel in the circumferential direction in the static reaction ring (10), and on the outside of the static reaction ring (10), a transport ring (30) having at least one slot (31) for receiving the reaction vessel (12) is arranged concentrically, the slot (31) being arranged at the same height as the slot (29) of the static reaction ring (10), and the transport ring (30) having at least one pusher (32) for transferring the reaction vessel (12) back and forth from the at least one slot (31) of the transport ring (30) to one of the slots (29) of the static reaction ring (10) by horizontal movement on the radial axis of the static reaction ring (10). The device according to any one of claims 1 to 7, characterized in that.
9. The transport ring has one, two, three or four slots (31) for receiving the reaction vessel (12), and pushers (32) arranged one by one in each slot (31) for transferring the reaction vessel (12) back and forth from the corresponding slot (31) of the transport ring (30) to one of the slots (29) of the static reaction ring (10) by horizontal movement on the radial axis of the reaction ring (10). The device according to claim 8, characterized in that.
10. There is at least one external slot (46) outside the transport ring (30) for receiving the reaction vessel (12), the at least one external slot (46) being at the same height as the at least one slot (31) for receiving the reaction vessel (12) of the transport ring (30), and the reaction vessel (12) can be transferred back and forth from the slot (31) of the transport ring (30) to the at least one external slot (46) for receiving the reaction vessel (12) by horizontal movement on the radial axis of the transport ring (30). The device according to any one of claims 8 or 9, characterized in that.
11. At least one of the measurement devices (14) is for measuring the optical properties of a liquid sample treated with a reagent in the reaction vessel (12), and the measurement device has a cylinder wall (34) and a cylinder top (35), and a rotatable transport cylinder (33) provided with at least one slot (36) for receiving the reaction vessel (12) in the cylinder wall. A cylindrical housing (37) having a cylindrical housing wall (38) and a cylindrical housing top (39), which is arranged concentrically around the transport cylinder (33), and at least one opening (43, 44) for inserting the reaction vessel (12) into the at least one slot (36) of the transport cylinder (33) and / or discharging it from the at least one slot (36) of the transport cylinder (33). The cylindrical housing (37) is provided. The device according to any one of claims 1 to 10, further comprising a photodetector (41) for detecting light emitted from the liquid in the reaction vessel (12) inserted into the at least one slot (36) of the transport cylinder (33).
12. The device according to claim 11, wherein the vertical fins (42) project upward or downward from the horizontal surface of the transport cylinder (33) and / or the cylindrical housing (37).
13. The device according to any one of claims 11 or 12, wherein the rotatable transport cylinder (33) has three slots (36, 36', 36''') for receiving the reaction vessel (12), and the slots (36, 36', 36''') are arranged in the cylinder wall (34) at an angle of 120°.
14. The measurement device (14) has a cylindrical housing (37), and the cylindrical housing (37) has one loading port (43) for inserting the reaction vessel (12) into the at least one slot (36) of the transport cylinder (33), and a reaction vessel (12). An outlet (44) for discharging from the at least one slot (36) of the transport cylinder (33), the loading port (43) is provided at the cylindrical housing top (39), and the outlet (44) is provided at the cylindrical housing wall (38). The device according to any one of claims 11 to 13.
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