Apparatus for automated diagnostic analysis of liquid samples

Abstract

In order to improve efficiency, minimize the size of the device and to reduce the workload of the operator running the analyzer, the present invention provides a device for the automatic diagnostic analysis of liquid samples, comprising a sample tray, at least two reagent trays, at least two reaction trays and at least two measuring devices, wherein the sample tray is arranged in the center of the analysis area, the at least two reaction trays are arranged adjacent to the sample tray, the at least two reagent trays are arranged adjacent to the reaction trays, the at least two measuring devices are arranged adjacent to the reaction trays, and wherein a pipetting device is arranged between the sample disc and each of the at least two reaction trays, and wherein a pipetting device is present between each of the at least two reagent trays and its corresponding reaction tray.

Description

Technical Field

[0001] The present invention relates to an apparatus for automated analysis of liquid samples, wherein the apparatus includes an analysis area comprising a sample tray for receiving sample containers, at least one reagent tray for receiving reagent containers, at least one reaction tray for receiving reaction dishes, and at least one measuring device for measuring the physical or chemical properties of liquid samples treated with reagents in the reaction dishes. Background Technology

[0002] Against the backdrop of increasing automation in the medical and veterinary diagnostic fields, devices for automated liquid analysis, known as analyzers, are becoming increasingly common. These analyzers are designed to automatically remove reagents from containers and combine them with the sample to be analyzed in a reaction dish to perform the analytical procedure. For this purpose, analyzers typically have sample trays, reagent trays, and reaction trays, which provide slots for receiving and holding the respective containers.

[0003] The steps of removing reagents or samples and transferring them to reaction dishes are typically performed by automated pipetting devices. Such automated pipetting devices generally include a pipetting arm with a pipetting needle connected to a pump unit for drawing liquid into the needle and discharging it again. The pipetting arm can move along the XY directions or by rotating over the working area containing the sample tray, reagent tray, and / or reaction tray.

[0004] Typically, an analyzer includes measuring devices for determining the physical or chemical parameters (process parameters) of the reaction mixture in a reactor dish. These measuring devices perform measurement techniques such as spectrophotometry, colorimetry, ion-selective electrodes, coagulation and immunoassays.

[0005] The area covered by the aforementioned diagnostic analysis apparatus is the analysis area, in which the sample tray, at least one reagent tray, at least one reaction tray, measuring device, and pipetting device for transferring liquids between other devices are located.

[0006] An example of an analyzer is disclosed in WO 2011 / 061118. To achieve the maximum possible sample throughput, the analyzer has exactly three rotatable disks (i.e., a sample disk, a reagent disk, and a reaction disk), at least three pipetting devices, and a measuring device. For the purpose of improving efficiency, the device operates in a continuous operating cycle in defined operating modes.

[0007] There is a need to continuously improve the automation efficiency of analyzers. Furthermore, there is a need to minimize the size of the equipment design to save space in the laboratory where the equipment will operate. Additionally, it is desirable to reduce the workload of the operators running the analyzers. Summary of the Invention

[0008] According to the present invention, the above-mentioned objectives are achieved by the following detailed description of various aspects, which generally share the common feature that the apparatus of the present invention includes an analytical region, characterized in that the analytical region 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 vessel; at least one measuring device for measuring the physical or chemical properties of the liquid sample treated with reagents in the reaction vessel; and at least one pipetting device for transferring the liquid sample from the sample container in the sample tray to the reaction vessel, and at least one pipetting device for transferring the reagent from the reagent container in the reagent tray to the reaction vessel.

[0009] As used in this invention, the term "sample" refers to any material prepared for the purpose of an analytical procedure and containing a substance to be analyzed for diagnostic purposes. Examples of samples are whole blood, purified blood, blood preserves, and other bodily fluids such as urine or alcohol.

[0010] The device of the present invention is capable of performing various analytical processes. In a preferred embodiment, the physical or chemical properties measured by at least one measuring device are selected from the results of immunoassays in a reactor dish, the results of clinical chemistry assays, the results of coagulation assays, or the results of ion-selective electrode assays.

[0011] Aspect 1: Component arrangement.

[0012] To improve efficiency, minimize equipment size, and reduce the workload of operators running the analyzer, this invention provides several technical solutions.

[0013] According to a first aspect of the present invention, an apparatus for automated analysis of liquid samples is disclosed, wherein the apparatus includes an analysis area, characterized in that the analysis area includes a sample tray for receiving sample containers, at least two reagent trays for receiving reagent containers, at least two reaction trays for receiving reaction vessels, and at least two measuring devices for measuring physical or chemical properties.

[0014] The sample tray is arranged at the center of the analysis area, at least two reaction trays are arranged adjacent to the sample tray, at least two reagent trays are arranged adjacent to the reaction trays, and at least two measuring devices are arranged adjacent to the reaction trays; and wherein a pipetting device is present between each of the sample trays and each of the at least two reaction trays for transferring liquid samples from sample containers in the sample trays to reaction dishes in the reaction trays, and wherein a pipetting device is present between each of the at least two reagent trays and their corresponding reaction trays for transferring reagents from reagent containers in the reagent trays to reaction dishes in the reaction trays.

[0015] According to a preferred embodiment, the device of the present invention is characterized in that: 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; at least two reaction trays are either in the form of rotatable reaction disks arranged adjacent to the sample trays, or in the form of static reaction rings; wherein, the pipetting device is in the form of a rotating pipetting arm, having a rotation axis at one end of the pipetting arm, and the other end of the pipetting arm can move along a circular path around the rotation axis, wherein the rotation axis of the pipetting device is located between the sample disk and each reaction disk / ring or between each reagent disk and its corresponding reaction disk / ring.

[0016] According to a first aspect of the invention, the sample tray is preferably provided in the form of a rotatable sample disk arranged at the center of the analysis region. The "analysis region" is the area of ​​the device of the invention, in which the sample tray, reagent tray, reaction tray, and pipetting device are located. In a preferred embodiment, the analysis region is a plane in which the devices are positioned side-by-side. The "center" of the analysis region is defined by a quadrilateral, pentagon, hexagon, or higher polygon formed by an imaginary straight line connecting the rotation axes of the reagent tray and the reaction tray. According to the invention, the sample tray is arranged in the center of the analysis region if the rotation axis of the sample tray passes through the center defined by the imaginary straight line connecting the rotation axes of the reagent tray and the reaction tray.

[0017] In this invention, the term "disc" refers to a circular tray that provides a groove for receiving liquid containers, such as sample containers, reagent containers, and reactor dishes. Conversely, the term "ring" refers to a specific circular liquid container tray in which, viewed from above, the ring expands between two concentric circles to form a central hole, the size of which is defined by the inner radius of the ring, wherein the inner radius of the ring is at least 30% of the outer radius of the ring.

[0018] In one embodiment, the sample tray is in the form of a sample disk having slots for receiving sample containers, the slots being arranged side-by-side along the outer periphery of the disk towards the edge. In an alternative embodiment, the sample tray is in the form of a sample disk having receiving recesses for receiving a longer sample container rack, the rack having 2 to 20 slots for receiving sample containers, the slots being arranged side-by-side along the central longitudinal axis of the rack, wherein the receiving recesses are radially oriented on the sample disk.

[0019] The "pipette" according to the invention includes a pipette connected to a pumping unit, which allows liquid to be drawn into and expelled from the pipette. In a preferred embodiment of the invention, the pipette includes a rotating pipette arm. A rotation axis is located at one end of the rotating arm, and the other end of the pipette arm can move along a circular path about this rotation axis, thereby defining the working area of ​​the pipette. Thus, the pipette can be moved to reagent containers, sample containers, and / or reaction dishes.

[0020] Preferably, the axis of rotation of at least one pipette is located between the sample disk and each reaction disk or reaction loop. Preferably, the axis of rotation of at least one other pipette is located between each reagent disk and its corresponding reaction disk or reaction loop.

[0021] Due to the component arrangement according to the specific aspects of the invention described above, at least two different diagnostic analytical procedures can be performed in the same analyzer. Specifically, immunoassays and clinical chemistry assays can be combined in the same analyzer, wherein two different analytical procedures can be performed because there are at least two reagent trays for receiving the reagent containers required for the respective analytical procedures. Further, there are two independent reaction trays for each analytical procedure, and at least two measuring devices are present according to the requirements of each procedure. Therefore, all these devices are provided at least in a duplex manner. However, only one sample tray is present, which is arranged in the center of the analytical area. Therefore, two different analytical procedures can be performed on samples provided in only one sample tray.

[0022] In a preferred embodiment of the invention, the analysis area is arranged in the housing, and in a more preferred embodiment, a loading opening is arranged in the housing of the device for receiving sample containers and reagent containers individually or in a pre-packaged rack form, wherein the loading opening includes a robotic arm for conveying the sample containers and reagent containers in the form of a pre-packaged rack from the loading opening to a sample tray and / or a reagent tray or conveying these sample containers and reagent containers individually.

[0023] The loading opening, including a robotic arm, provides the advantage of eliminating the need for the operator of the analytical apparatus to manually insert new samples and / or reagents into the sample or reagent trays. Typically, manually replacing samples and / or reagents requires stopping all movement within the analytical area to avoid any contact with moving parts such as pipette arms and / or rotating disks. Clearly, stopping all movement within the analytical area results in processing delays. Therefore, having a loading opening that includes a robotic arm for conveying sample and reagent containers to the sample and / or reagent trays is advantageous, as any movement of the robotic arm can be coordinated with any automated movement within the analytical area.

[0024] Furthermore, if needed, a robotic arm provides the beneficial effect of transferring liquid containers from one liquid container tray to another. For example, calibration liquids or reference standards are typically placed in sample containers on a sample tray to be included in the analytical process. However, between calibration steps where the sample containers containing the calibration liquids or reference standards must remain on the sample tray, it is preferable to allow the calibration liquids / reference standards to cool. For this purpose, a robotic arm can transfer sample containers containing calibration liquids / reference standards from a sample tray that is not normally cooled to one of a reagent tray that is normally cooled.

[0025] In some embodiments, the device includes an access control unit for coordinating access to the central sample tray by a robotic arm in the loading area and access to the central sample tray by analytical components arranged around it. Specifically, the control unit determines access rules and time slots taking into account different requesting units (robotic arm, analytical unit).

[0026] The control unit is connected to different components of the analyzer via a signal transmission connection device (such as via wires or Bluetooth). Through this connection, the robotic arm and analytical units (e.g., immunoassay unit, clinical chemistry unit) can communicate. Specifically, via this connection, the robotic arm and analytical units can request access to a central sample tray for a specified time period to place or remove sample containers or sample container racks from the tray, or to retrieve aliquots from sample containers placed in a sample disc. Preferably, when a time slot is needed, the time slot request is associated with a period attribute that defines a time period. More preferably, the time slot request is also associated with a priority attribute that defines at least two priorities (e.g., high / low), where a higher priority indicates that allocating a time slot within the specified time period is essential for correct operation, and a lower priority indicates that allocating a time slot within the specified time period is not essential for correct operation. The control unit then analyzes all requests, optionally including time period and / or priority attributes, and calculates an optimal operating profile for allocating a specific time slot for each access request. Finally, the relevant information for each time slot is communicated by the control unit to each requesting unit.

[0027] In embodiments where a housing is present, the housing is formed by a floor, a ceiling, a rear wall, side walls, and a front wall. In a preferred embodiment, a loading opening is arranged in the front wall of the housing. Preferably, the loading opening is arranged in the middle between the left and right edges of the front wall.

[0028] In some embodiments, the loading opening is designed to receive new sample containers and / or new reagent containers, which are placed in the loading opening individually by the analyzer operator or in the form of manually pre-packaged racks. A robotic arm can then pick up the container / rack and deliver it to the sample tray and / or reagent tray. Conversely, the robotic arm can remove empty containers / racks from the sample tray and / or reagent tray and deliver them to the loading opening, where the operator can remove them. Therefore, the “loading opening” of this invention is not only a “loading opening” but also an “unloading opening.”

[0029] In one specific embodiment of the invention, the device includes a conveyor for individually or in the form of pre-packaged racks conveying sample containers and / or reagent containers to or from a loading opening. The conveyor extends horizontally along the wall of the housing where the loading opening is arranged, extending from the loading opening to the left and / or right side.

[0030] In this application, the term "loading opening" refers to an area within the wall of the device in which sample / reagent containers / racks can be placed by an operator or by a conveyor for pickup by a robotic arm. Conversely, the term "loading area" refers to an area above the conveyor outside the loading opening in which an operator can place sample / reagent containers / racks.

[0031] In some embodiments, one end of the conveyor is outside the loading opening, while the other end reaches into the loading opening. A loading area is located at the end outside the loading opening, in which multiple sample containers and / or reagent containers can be placed individually or in the form of pre-packaged racks on the conveyor. The conveyor then transports the containers / racks one by one into the loading opening. Further, such a conveyor allows used or even empty sample containers and / or reagent containers that have been removed from the sample or reagent disc and placed into the loading opening by a robotic arm to the outer end of the conveyor. In these cases, the conveyor is bidirectional, and the loading area is also the unloading area.

[0032] In other embodiments, one end of the conveyor is outside the left side of the loading opening, while the other end of the wall-mounted conveyor passes through the loading opening and extends to the right side. In those embodiments, the loading and unloading areas of the conveyor are separate, i.e., a loading area exists on one side from the loading opening, and an unloading area exists on the opposite side.

[0033] In one embodiment, two separate conveyors exist on the same horizontal plane, one on the left and one on the right, which converge at the loading opening. In another embodiment, three separate conveyors exist on the same horizontal plane, one starting from the left side of the loading opening, one starting from the right side of the loading opening, and one located inside the loading opening.

[0034] In a particular embodiment, at least one horizontal conveyor extends to the edge of the wall of the analyzer housing, with a loading opening located at that edge. The conveyor is used to individually transfer liquid containers, or liquid containers placed on a shelf, to a second analyzer located adjacent to the edge of the wall of the analyzer housing. If the second analyzer is an analyzer according to the invention, including a conveyor extending from the edge of the wall of the analyzer housing to the loading opening, the liquid container can be transferred from the first analyzer to the second analyzer for further analysis.

[0035] In a specific embodiment, two or more analyzers of the present invention share a single transmitter or a combination of multiple horizontally aligned transmitters for individually transferring liquid containers or liquid containers placed on a shelf from one analyzer to another.

[0036] The term "robotic arm" refers to a movable transport device with end effectors for transporting sample containers and / or reagent containers individually or in the form of a rack containing sample containers and / or reagent containers. In one embodiment, the robotic arm has a rotating element with an axis of rotation passing through one end of the rotating element. About the axis of rotation, i.e., relative to the axis of rotation, end effectors arranged at opposite ends of the rotating element can move along a circular path.

[0037] In another preferred embodiment, the rotating arm can move along a vertical axis, and in another preferred embodiment, the rotating element or the entire robot arm can move along a horizontal axis. Specifically, it is preferred that the rotating element can move along both the vertical and horizontal axes.

[0038] All potential movements about the axis of rotation, along the vertical axis, and along the horizontal axis define the working area of ​​the robotic arm, in which the end effector can move to loading openings for sample containers and / or reagent containers, as well as slots for receiving sample containers or reagent containers in sample trays and / or reagent trays. To minimize the required working area, it is preferable to position the axis of rotation between the sample disk and at least two reagent disks.

[0039] In a specific embodiment, the robotic arm includes an end effector having at least two fingers movable relative to each other for individually or in the form of a pre-packaged rack to grasp and transport sample containers and reagent containers.

[0040] In specific embodiments of the invention, the housing of the analytical device includes a base and an openable cover, wherein the analytical region is arranged on top of the base, and the cover completely covers the analytical region in its closed state. In those embodiments, the loading opening is preferably arranged in the front wall of the base or in the cover, or extends across both the front wall of the base and the cover.

[0041] Regardless of which of the above alternatives is implemented, the loading opening allows samples and / or reagents to be loaded into the analytical device without opening the cover. Furthermore, samples and / or reagents can be placed in the loading opening at any time. There is no need to wait for a specific time period when samples and / or reagents can be loaded into the analyzer. Whenever a time period exists for loading a corresponding tray into the analyzer, the robotic arm can grab the sample or reagent from the loading area and transport it to the corresponding tray.

[0042] To differentiate samples and different reagents, sample and reagent containers can be tagged with one-dimensional barcodes, two-dimensional barcodes (matrix codes), or RFID (Radio Frequency Identification) tags. Therefore, in a preferred embodiment, a one-dimensional barcode reader, a two-dimensional barcode reader, and / or an RFID reader are provided in the loading area to identify samples and / or reagents placed in the loading area by the operator. Before conveying the container to the target location, the robotic arm moves the grasped container to the reader and performs the corresponding conveying action based on the information read from the code.

[0043] In a preferred embodiment, the control unit is connected to a barcode reader, QR code reader, and / or RFID reader in the loading area via a signal transmission connection device (such as via wires or Bluetooth). Through this connection device, the control unit can receive information about the various containers placed in the loading opening. Based on this information, the control unit can determine whether to place the container in a sample disk or a reagent disk. The control unit then transmits information about the designated location of the container to the robotic arm.

[0044] In some embodiments, each reagent container is individually placed into a loading opening or onto a conveyor. In other embodiments, the reagent container is placed on a reagent container rack, which is then placed into a loading opening or onto a conveyor. Alternatively, a robotic arm grasps the reagent container but leaves the reagent rack on the conveyor, or the robotic arm grasps the entire rack including the reagent container. The same alternative applies to grasping sample containers / sample container racks.

[0045] In some embodiments, the sample tray, reagent tray, reaction tray, and loading opening are elements surrounded by a single housing. However, in some embodiments, the housing consists of physically separable units, wherein, respectively, one unit includes the sample tray and the loading opening, and other units include a combination of the reagent tray and the reaction tray, as well as a measuring device.

[0046] The physically separate units have individual housings designed for fixed assembly to form a compact analytical device having a sample tray, at least two reagent trays, at least two reaction trays, and at least two measuring devices arranged on top of the compact analytical device. Preferably, a cover is provided hinged to the top of the compact analytical device, wherein the cover covers the entire top of the analytical device, i.e., including all its units.

[0047] In some embodiments, there is a combination of one immunoassay unit and one clinical chemistry unit. In other embodiments, there is a combination of two immunoassay units or two clinical chemistry units. In some embodiments, there are 3, 4, 5, 6, 7 or even 8 units in the combination, wherein for each combination of two units, a loading area is provided to serve the combination of said two units.

[0048] In a preferred embodiment of the invention, the device is arranged in the analyzer in accordance with at least one of the following symmetry rules: the axis of rotation of the sample disk is on the center line between the side walls relative to the side walls of the analyzer housing; the center line of the loading opening is located on the center line between the side walls relative to the side walls of the analyzer housing; the center position of the robotic arm is on the center line of the loading opening; the axes of rotation of the first reagent disk on one side and the second reagent disk on the other side are at the same distance from the center line between the side walls of the analyzer housing; the axes of rotation of the first reaction disk or transport ring on one side and the second reaction disk or transport ring on the other side are at the same distance from the center line between the side walls of the analyzer housing; the axes of rotation of the first reaction disk or transport ring on one side and the second reaction disk or transport ring on the other side are relative to the center line between the side walls of the analyzer housing. The centerlines between the sidewalls of the instrument housing are at the same distance; the rotation axis of the first rotary pipette between the first reagent disk and the corresponding reaction disk / ring on one side, and the rotation axis of the second rotary pipette between the second reagent disk and the corresponding reaction disk / ring on the other side, are at the same distance from the centerline between the sidewalls of the analyzer housing; the rotation axis of the first rotary pipette between the sample tray and the first reaction disk / ring on one side, and the rotation axis of the second rotary pipette between the sample tray and the second reaction disk / ring on the other side, are at the same distance from the centerline between the sidewalls of the analyzer housing.

[0049] Arranging the device within the analyzer according to one or more of the following symmetry rules allows for easy replacement of the immunoassay unit with the clinical chemistry unit, and vice versa.

[0050] In cases where the sample tray is a sample disk, the diameter of the disk is in the range of 30 to 60 cm. In cases where the reagent tray is a reagent disk, the diameter of the disk is in the range of 30 to 60 cm. In cases where the reaction tray is a reaction disk / ring, the diameter of the disk is in the range of 30 to 60 cm.

[0051] 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 in the sense of defining the shortest distance between the outer edges of the two devices, wherein the distance should be in the range of 5 to 15 cm, preferably in the range of 5 to 10 cm.

[0052] According to the present invention, the pipetting device is located either between the sample tray and each reaction tray, or between each reagent tray and its corresponding reaction tray. The term "between" should be understood in the sense that the working area of ​​the pipetting device located between the two devices allows movement to the containers in said two devices.

[0053] In a preferred embodiment of the rotary pipette, the working area of ​​the rotary pipette has a radius ranging from 5 to 15 cm. Within this radius, the pipette needle, located, for example, between a sample disk and a reaction disk, can move to both the sample container in the sample disk and the reaction vessel in the reaction disk.

[0054] A second aspect of the invention: a static reaction loop. When performing an immunoassay, the reaction mixture needs to be cultured under specified conditions to allow time for the target molecule to react with the antibody. Specifically, the culture is performed under specific temperature conditions. Therefore, the reaction dish containing the reaction mixture is typically placed in a constant-temperature incubator for a specific period of time.

[0055] According to one aspect of the invention, an analyzer comprising an immunoassay unit is provided, wherein culture is performed in a reaction tray provided in the form of a static reaction loop. The static reaction loop has culture tanks for receiving reaction dishes, wherein the tanks are arranged side-by-side on the loop. A transport ring is concentrically arranged outside the static reaction loop, the transport ring having at least one transport tank for receiving and transporting reaction dishes, wherein the transport tank is arranged on the same horizontal plane as the tanks in the static reaction loop. The transport ring has at least one actuating element for transferring the reaction dishes from at least one transport tank in the transport ring to one of the culture tanks in the static reaction loop and back by horizontal movement along the radial axis of the reaction loop.

[0056] According to a preferred embodiment of the invention, the groove in the static reaction ring is made of metal. Preferably, the static reaction ring is a single piece of metal having a groove for receiving the reactor vessel as an integral part of it.

[0057] In a specific embodiment of the invention, the static reaction ring has a single row of grooves arranged circumferentially side-by-side at the outer circumferential edge of the ring. In an alternative embodiment, the static reaction ring has a first row of grooves arranged circumferentially side-by-side on the outer circumferential edge of the ring and a second row of grooves arranged circumferentially adjacent to each other in a direction pointing towards the central axis of the ring.

[0058] To warm the static reaction ring, a heating device is provided for heating a metal tank or a single metal ring comprising the tank as an integral part thereof. The heating device has means for controlling and maintaining the temperature of the static reaction ring within a range of 20 to 50°C.

[0059] In some embodiments, the reaction vessel is a cuvette having a base region, a long side, and a short side, wherein the long side of each cuvette is oriented along the radial axis of the reaction disk. Therefore, the long side of the groove in the static reaction ring is oriented along the radial axis of the static reaction ring.

[0060] The conveying ring is rotatably arranged around the stationary reaction ring, and the conveying ring has 1, 2, 3 or 4 slots for receiving the reactor vessel, and the conveying ring has a pusher at each slot for transferring the reactor vessel from the corresponding slot in the conveying ring to one of the slots in the stationary reaction ring and back by horizontal movement along the radial axis of the reaction ring.

[0061] In some specific embodiments of the invention, at least one external groove for receiving the reactor vessel is provided in the radial direction outside the conveying ring. This external groove is on the same horizontal plane as the conveying groove in the conveying ring for receiving and conveying the reactor vessel, allowing the reactor vessel to be transferred from a groove in the conveying ring to the external groove and back via horizontal movement along the radial axis of the conveying ring. In those embodiments, the conveying ring has at least one pusher for transferring the reactor vessel from at least one conveying groove in the conveying ring to one of the external grooves via horizontal movement along the radial axis of the conveying ring.

[0062] The aforementioned external tank serves as a storage location for further processing of the reaction mixture within the reactor vessel, such as for bead separation, for coagulation determination, for mixing, or for cleaning the reactor vessel.

[0063] To maintain the temperature within the circular static reaction ring and prevent the heated reaction ring from raising the temperature of the reaction mixture in a reactor vessel positioned in an outer tank, a circular thermal isolation shell is provided around the reaction ring. The cross-section of the circular isolation shell has the shape of an inverted letter "U".

[0064] A third aspect of the invention: a circular measuring chamber. According to a third aspect of the invention, an analytical apparatus is provided having at least one measuring device for measuring the optical properties of a liquid sample treated with a reagent in a reactor dish, wherein the measuring device comprises a rotatable conveying cylinder having a wall and a top, wherein at least one groove is provided in the wall for receiving the reactor dish; a cylindrical shell having a wall and a top, the cylindrical shell being concentrically arranged around the conveying cylinder, wherein at least one opening is provided for inserting or ejecting the reactor dish from at least one groove in the conveying cylinder; and a photodetector for detecting light emitted from the liquid in the reactor dish, the reactor dish being inserted into at least one groove in the conveying cylinder.

[0065] By rotating the conveyor cylinder, at least one trough for receiving the reactor vessel can move from the loading position to the detection position and further to the ejection position. In some embodiments, at least one processing position is also provided, at which reagents are added to the reaction mixture, wherein, in the direction of movement, such a processing position is between the loading position and the detection position.

[0066] The cylindrical shell and conveyor tube are designed to provide a loading opening for loading the reactor dish into at least one slot when the conveyor tube is in the loading position for at least one slot. The cylindrical shell and conveyor tube are also designed to provide an ejection opening for ejecting the reactor dish from at least one slot when the conveyor tube is in the ejection position for at least one slot. Furthermore, the cylindrical shell and conveyor tube are designed such that, when the at least one slot is in the light detection position, the conveyor tube holds the reactor dish in the at least one slot directly in front of the light opening located on the wall of the cylindrical shell, such that light emitted from the liquid in the reactor dish can reach a light detector arranged on the other side of the light opening through the light opening.

[0067] The circular measuring chamber of this invention is specifically designed for measuring the optical properties of liquid samples under conditions where the intensity of the light to be detected is relatively low and / or must be precisely quantified. An example of a determination where the intensity of the light to be detected is relatively low and / or must be precisely quantified is CLIA (chemiluminescent immunoassay). In this case, the measurement needs to be performed in absolute darkness to avoid any photons from the outside potentially reaching the detector.

[0068] In this case, the specific photodetector that provides the required sensitivity can be selected from a PMT detector with a photomultiplier tube.

[0069] The rotatable conveyor tube is precisely fitted into the cylindrical housing, creating a very small gap when the conveyor tube rotates within the housing, thus providing minimal backlash. In some embodiments, the maximum distance between the outer periphery of the conveyor tube wall and the inner periphery of the cylindrical housing wall is 1 mm or less. This is to ensure an opaque arrangement so that light that may enter the loading position when the reactor vessel is loaded into the conveyor tube can reach the photodetector located at the detection position.

[0070] The number of slots in the conveying cylinder wall is preferably 1, 2, or 3. In those embodiments, where there are two slots in the conveying cylinder, the two slots are arranged at opposite positions on the outer circumferential edge of the conveying cylinder, i.e., at an angle of 180° to each other. In those embodiments where the rotatable conveying cylinder has three slots for receiving the reactor vessel, the slots are preferably arranged in the cylinder wall at the outer circumferential edge of the conveying cylinder, at an angle of 120° relative to the corresponding adjacent slot.

[0071] By orienting the slots in the manner described above, the risk of photons reaching the detection position from the loading position is minimized. Furthermore, in a preferred embodiment of the invention where vertical fins protrude upwards or downwards from the horizontal surface of the conveyor cylinder and / or cylindrical housing, the risk of any photons reaching the detection opening from the loading opening is minimized.

[0072] In some embodiments, a plurality of vertical fins extend linearly and parallel to each other from one edge of a respective surface to the opposite edge of the surface. In a particular embodiment, a first set of vertical fins extends linearly and parallel to each other from one edge of a respective surface to the opposite edge of the surface, and a second set of fins, also extending linearly and parallel to each other from one edge of a respective surface to the opposite edge of the surface, passes through the first set of fins at an angle ranging from 30° to 90°.

[0073] In other specific embodiments, the vertical fins are arranged in a concentric circle, and in a very specific embodiment, the vertical fins are arranged in a concentric circle that protrudes upward from the outer surface of the top of the conveying cylinder and / or downward from the inner surface of the top of the cylindrical shell, wherein the fins are arranged concentrically around the rotation axis of the conveying cylinder.

[0074] In some embodiments, the cross-section of the fins is rectangular, triangular, semi-circular, or a combination thereof. In a particular embodiment, where fins are present on opposing surfaces, such as the outer surface of the top of the conveyor cylinder and the inner surface of the cylindrical shell, the fins can be designed to match each other, wherein adjacent fins are either peak-to-peak aligned or interlocked such that the peak of a fin on one surface reaches into the gap between fins on the other surface, and vice versa.

[0075] Another embodiment is characterized in that the cylindrical shell has a loading opening in a groove for inserting the reactor vessel into the delivery cylinder and an unloading opening for ejecting the reactor vessel from at least one groove in the delivery cylinder, wherein the loading opening is located at the top of the cylindrical shell and wherein the unloading opening is located in the wall of the cylindrical shell.

[0076] For the purposes of the original disclosure, it should be noted that any feature gleaned from this specification, drawings, and claims by a person skilled in the art, even if described only in conjunction with specific further features, can be combined individually and in any combination with any other feature or group of features disclosed herein, unless such combination is expressly excluded or technical conditions would render such combination impossible or meaningless. A full and explicit discussion of any possible combinations of features has been omitted merely for the sake of brevity and readability of the description and claims.

[0077] Specifically, it should be noted that features mentioned in the context of one of the above aspects of the invention may be combined with features mentioned in the context of another aspect of the invention.

[0078] Furthermore, it should be noted that the following figures and detailed description are merely illustrative of possible constructions of the invention, i.e., illustrated by way of example. Therefore, those skilled in the art will readily understand that all other structures having features or combinations thereof according to the invention as described in the claims also fall within the scope of protection of the invention. A full and clear representation of all conceivable embodiments has been omitted herein for the sake of brevity and readability. Attached Figure Description

[0079] In the appendix Figures 1 to 4 middle:

[0080] Figure 1 A perspective view of the top of a specific embodiment of the analyzer of the present invention is shown.

[0081] Figure 2 Details of the static reaction loop of a specific embodiment of the analyzer of the present invention are shown.

[0082] Figure 3 A perspective view of the circular measuring chamber of a specific embodiment of the analyzer of the present invention is shown.

[0083] Figure 4 Specific embodiments of the analyzer without the present invention are shown. Figure 3 A circular measuring chamber. Detailed Implementation

[0084] Figure 1The diagram shows a perspective view of the top of a specific embodiment of the analyzer 1 of the present invention, viewed from above. In the analysis area 2 of the analyzer 1, there are two reagent trays 5 and 6, both of which are rotary disks. Further, in the analysis area 2, there are two reaction trays 9 and 10, wherein one reaction tray 9 is a rotatable reaction disk, and the other reaction tray 10 is a static reaction ring 10.

[0085] The center of the analytical region 2 is defined by a rectangle formed by the dashed line connecting the rotation axes of reagent disks 5 and 6 and the rotation axes of reaction disks 9 and 10. The rotation axis of the sample tray 3 passes through the center of the analytical region 2. Therefore, the sample tray 3 is positioned at the center of the analytical region 2.

[0086] Adjacent to sample tray 3, two reagent trays 5 and 6 are located on the right and left sides of sample tray 3, respectively. Further, adjacent to sample tray 3, two reaction trays 9 and 10 are located, one on the right and one on the left.

[0087] Pipettes 15 and 16 are present between sample tray 3 and each of the two reaction trays 9 and 10. Further, two pipettes 17 are present between reaction tray 9 and reagent tray 5, and one pipette 18 is present between reaction tray 10 and reagent tray 6. Further, the two pipettes 15 and 17 between sample tray 3 and reaction trays 9 and 10 are used to transfer liquid samples from sample containers 4 in sample tray 3 to reaction dishes 11 and 12 in reaction trays 9 and 10. The pipettes 17 and 18 between reagent trays 5 and 6 and reaction trays 9 and 10 are used to transfer reagents from reagent containers 7 and 8 in reagent trays 5 and 6 to reaction dishes 11 and 12 and reaction trays 9 and 10.

[0088] The pipetting devices 15, 16, 17, and 18 are in the form of rotating pipette arms, each having a rotation axis 19 at one end. The pipette needle 20 at the other end of the pipette arm can move along a circular path around this rotation axis. The rotation axis 19 of the pipetting devices 15, 16, 17, and 18 is located either between the sample tray 3 and each reaction tray 9, 10, or between each reagent tray 5, 6 and its corresponding reaction tray 9, 10.

[0089] Measuring devices 13 and 14 are adjacent to each of reaction trays 9 and 10. Measuring device 14, adjacent to reaction tray 10, is a PMT detector with a photomultiplier tube for measuring chemiluminescence in immunoassays. Measuring device 13, adjacent to reaction tray 9, is a photometer for measuring the optical properties of clinical chemistry reaction mixtures. Sample tray 3 has receiving recesses 28 for receiving longer sample racks 24, each rack having five slots for receiving sample containers 4, the five slots being arranged side-by-side along the longitudinal axis of the rack. The receiving recesses 28 are radially oriented on sample tray 3. In this embodiment, there are ten receiving recesses 28. Therefore, sample tray 3 of this embodiment can hold ten sample racks when full, each with five slots. Thus, sample tray 3 can hold a maximum of 50 sample containers in total.

[0090] The reagent tray 6 has 14 receiving recesses for receiving reagent racks, each of which has 3 slots for receiving reagent containers 8. The reagent racks are radially positioned on the outer circumferential edge of the reagent tray 6.

[0091] The reagent tray 5 has 24 recesses for receiving reagent racks 23, and each of the reagent racks has two slots for receiving reagent containers 7. The recesses for receiving reagent racks are arranged in two rows, one row on the outer peripheral edge of the reagent tray 5 and the other row in the center of the reagent tray 5.

[0092] The reaction tray 9 has approximately 100 slots on its outer circumferential edge for receiving reaction dishes 11. In this embodiment, the reaction dishes are cuvettes for photometric analysis of the reaction mixture contained therein. By rotating the reaction tray 9, each reaction dish 11 can be fed to a photometer 13 to measure the optical properties of the reaction mixture contained therein.

[0093] The reaction tray 10 is a static reaction ring, and a conveying ring 30 is concentrically arranged outside the static ring for conveying the reactor vessel 12 to and from the static reaction ring 10.

[0094] according to Figure 1The illustrated embodiment of analyzer 1 has an analytical area arranged on a plane and inside a housing 21, wherein the housing 21 has a loading opening 22 in the front wall of the housing 21. The loading opening 22 is used to individually receive sample containers 4 and reagent containers 7, 8, or to receive sample containers 4 and reagent containers 7, 8 pre-packaged in reagent racks 23 or sample racks 24. The loading opening 22 includes a robotic arm 25 for individually or in the form of pre-packaged reagent racks 23 or sample racks 24 conveying sample containers 4 and reagent containers 7, 8 from the loading opening 22 to sample trays 3 or reagent trays 5, 6. Further, the robotic arm 25 can convey sample containers from sample tray 3 to reagent trays 5, 6 and back. In those embodiments where reagent trays 5, 6 are cooled, sample racks 24 carrying sample containers filled with reference standards can be transferred to reagent trays 5, 6 for cooling to extend the lifespan of the reference standards.

[0095] In the illustrated embodiment, robotic arm 25 is a rotary arm having a rotation axis at one end and the other end movable along a circular path about the rotation axis. At the ends of the arm on opposite sides of the rotation axis, the robotic arm has end effectors for grasping and conveying sample containers and reagent containers individually or in the form of pre-packaged racks.

[0096] The robotic arm can move along a horizontal axis from left (where reagent tray 6 is located) to right (where reaction tray 5 is located) to place reagent containers / racks onto or remove reagent containers / racks from reagent trays 5 or 6. Furthermore, the robotic arm 25 can move along a vertical axis to pick up containers / racks from the horizontal plane (horizontal height) of the loading opening 22, which is lower than the horizontal plane of the analysis area 2, and transport the containers / racks to the horizontal plane of the analysis area, placing them, for example, into reagent trays 5 or 6.

[0097] The circular motion of the rotating arm, combined with its mobility along the horizontal and vertical axes, allows the robotic arm 25 to move the end effector within the work area, whereby the end effector can individually or in the form of a pre-packaged rack, grasp sample containers and / or reagent containers from the loading opening 22, reagent trays 5, 6 and / or sample tray 3, deliver or transfer them from one of the devices to another, and / or place or insert them into one of the devices.

[0098] A horizontal recess is provided in the front wall of the housing 21, which provides a conveyor 27 that passes from left to right through a loading opening 22. Containers / racks to be loaded into sample trays 3 and / or reagent trays 5, 6 can be placed on the conveyor 27, which transports the containers / racks to the loading opening 22, where a robotic arm 25 can pick up the containers / racks and carry them into the analysis area.

[0099] Figure 2 Details of the static reaction ring 10 of a specific embodiment of the analyzer 1 of the present invention are shown. The static reaction ring 10 has a groove 29 for receiving a reactor dish 12, wherein the grooves 29 are arranged circumferentially side-by-side on the static reaction ring 10. A transport ring 30 is concentrically arranged outside the static reaction ring 10, and the transport ring has a groove 31 for receiving the reactor dish 12, wherein the groove 31 and the grooves 29 in the static reaction ring 10 are arranged on the same horizontal plane. Therefore, a pusher 32 arranged on the transport ring 30 can transfer the reactor dish 12 from the groove 31 of the transport ring to one of the grooves 29 in the static reaction ring 10 by horizontal movement along the radial axis of the static reaction ring 10. This pusher 32 can also remove the reactor dishes 12 from the grooves 29 in the static reaction ring and transfer them to the transport groove 31 and the transport ring 30.

[0100] exist Figure 2 In a specific embodiment, an outer groove 46 exists outside the conveying ring. The outer groove 46 is used to receive the reactor vessel 12, and the reactor vessel 12 can be placed in the outer groove 46 by a pusher 32 by moving horizontally directly from the conveying ring 13 or by moving horizontally from the static reaction ring 10 through the conveying ring 30 to reach the outer groove 46.

[0101] exist Figure 2 In this embodiment, the outer tank 46 is a resting position for further processing of the reaction mixture placed in the reactor vessel 12 at the resting position. This further processing may be, for example, a mixing step, a magnetic bead separation step, or some other further processing step.

[0102] In the specific embodiment shown, the static reaction ring 10 has a single row of grooves 29 arranged circumferentially side by side at the outer peripheral edge of the ring.

[0103] Figure 3 and 4 A circular measuring chamber is shown according to a specific embodiment of the analyzer according to the present invention. Figure 3 Specifically, a perspective view of the circular measuring chamber, including the cylindrical housing 37, is shown. Figure 4 The same measuring chamber without the cylindrical housing 37 is shown.

[0104] Figure 3 and 4 The measuring device 14 is used to measure the optical properties of a liquid sample treated with a reagent in a reactor dish 12. The measuring device 14 includes a rotatable delivery tube 33 surrounded by a cylindrical housing 37. A photodetector 41 is located on one side of the measuring device 14 for detecting light emitted from the liquid in the reactor dish 12, which has been inserted into one of the slots 36 of the delivery tube 33.

[0105] The rotatable conveying cylinder 33 has a cylinder wall 34 and a cylinder top 35, wherein the cylinder wall 34 has three slots 36 for receiving the reactor dish 12. In the illustrated embodiment, the three slots 36 for receiving the reactor dish 12 are arranged in the cylinder wall at an angle of 120°.

[0106] The conveying cylinder 33 is rotatable and is surrounded by a cylindrical shell 37. The cylindrical shell 37 has a cylindrical shell wall 38 and a cylindrical shell top 39, and the cylindrical shell 37 is arranged concentrically around the conveying cylinder 33, wherein there is an opening 43 for inserting the reactor dish 12 into the groove 36 in the conveying cylinder 33, and an opening 44 for ejecting the reactor dish 12 from the groove 36 in the conveying cylinder 33.

[0107] exist Figure 3 and 4 In the illustrated embodiment, vertical fins 42 protrude upward from the top 35 of the conveyor cylinder. The vertical fins 42 are arranged concentrically in a circle about the axis of rotation of the conveyor cylinder 33. Further, the fins 42 have a triangular cross-section and they mate with adjacent fins arranged on opposite surfaces of the top 39 of the cylindrical housing. Specifically, adjacent fins engage with each other because the peaks of the fins on one surface reach into the gaps between the fins on the other surface, and vice versa.

[0108] Figure label:

[0109] 1. Equipment (analyzer) for automated diagnostic analysis of liquid samples;

[0110] 2. Analysis area;

[0111] 3. Sample tray;

[0112] 4. Sample containers;

[0113] 5. First reagent disk;

[0114] 6. Second reagent disk;

[0115] 7. First reagent container;

[0116] 8. Second reagent container;

[0117] 9. Reaction disk;

[0118] 10. Reaction ring;

[0119] 11. First reactor dish;

[0120] 12. Second reactor vessel;

[0121] 13. First measuring device;

[0122] 14. Second measuring device;

[0123] 15. First pipetting apparatus;

[0124] 16. Second pipetting device;

[0125] 17. First pipetting apparatus;

[0126] 18. Second pipetting device;

[0127] 19. Axis of rotation;

[0128] 20 pipettes;

[0129] 21. Shell;

[0130] 22 Loading opening;

[0131] 23. Reagent rack;

[0132] 24 Sample racks;

[0133] 25 robotic arms;

[0134] 27. Conveyor;

[0135] 28. Recesses for receiving sample holders;

[0136] 29. A trough for receiving the reactor vessel;

[0137] 30 Conveyor ring;

[0138] 31. A trough for receiving the reactor vessel;

[0139] 32. Pushing component;

[0140] 33. Conveyor cylinder;

[0141] 34. Cylinder wall;

[0142] 35. Top of the cylinder;

[0143] 36. A trough in the cylinder wall for receiving the reactor vessel;

[0144] 37. Cylindrical shell;

[0145] 38. Cylindrical shell wall;

[0146] 39. Top of cylindrical shell;

[0147] 41. Photodetector;

[0148] 42. Vertical fins;

[0149] 43 Loading opening for inserting the reactor vessel;

[0150] 44 Unloading opening for ejecting the reactor vessel;

[0151] 45. Sidewall;

[0152] 46. ​​External trough for receiving the reactor vessel.

Claims

1. An automated analysis device for liquid samples, wherein, The device includes an analysis area, characterized in that the analysis area includes a sample tray for receiving sample containers, at least two reagent trays for receiving reagent containers, at least two reaction trays for receiving reaction vessels, and at least two measuring devices for measuring physical or chemical properties. -The sample tray is arranged in the center of the analysis area. - The at least two reaction trays are arranged adjacent to the sample tray. -The at least two reagent trays are arranged adjacent to the reaction tray, and - The at least two measuring devices are arranged adjacent to the reaction tray. The sample tray and each of the at least two reaction trays are provided with a pipetting device for transferring liquid samples from sample containers in the sample tray to reaction dishes in the reaction tray, and the reagent trays and their corresponding reaction trays are provided with a pipetting device for transferring reagents from reagent containers in the reagent tray to reaction dishes in the reaction tray, wherein the analysis area is arranged in a housing having a loading opening for individually receiving sample containers and reagent containers or receiving sample containers and reagent containers pre-packaged in a sample rack or reagent rack, wherein the loading opening includes a robotic arm for conveying the sample containers and reagent containers individually or in the form of a pre-packaged sample rack or reagent rack from the loading opening to the sample tray or the reagent tray.

2. The device as described in claim 1, characterized in that, - The sample tray is in the form of a rotatable sample disk. -The at least two reagent trays are in the form of rotatable reagent discs. - The at least two reaction trays are either in the form of rotatable reaction disks arranged adjacent to the sample tray, or in the form of static reaction rings. -The pipetting device is in the form of a rotating pipetting arm, with a rotation axis around the pipetting arm at one end, and the pipetting needle at the other end of the pipetting arm can move along a circular path around the rotation axis, wherein the rotation axis of the pipetting device is located between the sample disk and each reaction disk or static reaction ring or between each reagent disk and its corresponding reaction disk or static reaction ring.

3. The device as described in any one of claims 1 and 2, characterized in that, The loading opening is arranged in the front wall of the housing.

4. The device as described in claim 1, characterized in that, The loading opening includes a barcode, QR code, and / or RFID reader.

5. The device as described in claim 1, characterized in that, The device includes a conveyor for individually or in the form of pre-packaged racks conveying sample containers and / or reagent containers to or from the loading opening.

6. The device as described in claim 1, characterized in that, The physical or chemical properties measured by at least one of the at least two measuring devices are the result of an immunoassay, a clinical chemistry assay, a coagulation test, or an ion-selective electrode assay.

7. The device as described in claim 2, characterized in that, The sample disk has receiving recesses for receiving a longer sample holder, the sample holder having 2 to 20 slots for receiving the sample container along the central longitudinal axis of the sample holder, wherein the receiving recesses are radially oriented on the sample disk.

8. The device as described in claim 1, characterized in that, At least one of the reaction trays is in the form of a static reaction ring having a groove for receiving the reactor vessel, the grooves being arranged circumferentially side-by-side on the static reaction ring. Concentrically arranged transport rings are located outside the static reaction ring, each transport ring having at least one groove for receiving the reactor vessel. The grooves in the transport rings are arranged on the same horizontal plane as the grooves in the static reaction rings. The transport rings also have at least one pusher for transferring the reactor vessel from at least one groove in the transport rings to one of the grooves in the static reaction rings and back by horizontal movement along the radial axis of the static reaction rings.

9. The device as described in claim 8, characterized in that, The conveying ring has one, two, three, or four slots for receiving the reactor vessel and a pusher arranged on each slot in the conveying ring for transferring the reactor vessel from the corresponding slot in the conveying ring to one of the slots in the static reaction ring and returning it by horizontal movement along the radial axis of the static reaction ring.

10. The device as claimed in any one of claims 8 and 9, characterized in that, There is at least one external slot outside the conveying ring for receiving the reactor vessel, the at least one external slot being on the same horizontal plane as at least one slot in the conveying ring for receiving the reactor vessel, such that the reactor vessel can be transferred from the slot in the conveying ring to the at least one external slot for receiving the reactor vessel by horizontal movement along the radial axis of the conveying ring and then returned.

11. The device as claimed in claim 1, characterized in that, At least one of the measuring devices is used to measure the optical properties of a liquid sample treated with a reagent in a reactor dish, wherein the measuring device includes - A rotatable conveying cylinder having a cylindrical wall and a cylindrical top, wherein at least one groove is provided in the cylindrical wall for receiving a reactor vessel. - A cylindrical shell having a cylindrical shell wall and a cylindrical shell top, the cylindrical shell being concentrically arranged around the rotatable conveying cylinder, wherein at least one opening is provided for inserting or ejecting a reactor dish from at least one slot in the rotatable conveying cylinder, and - A light detector for detecting light emitted from a liquid in a reactor dish inserted into at least one slot of the rotatable conveyor cylinder.

12. The device as claimed in claim 11, characterized in that, Vertical fins protrude upwards or downwards from the horizontal surface of the rotatable conveyor cylinder and / or cylindrical housing.

13. The device as claimed in any one of claims 11 and 12, characterized in that, The rotatable conveyor cylinder has three slots for receiving the reactor vessel, the slots being arranged at a 120° angle in the cylinder wall.

14. The device as claimed in claim 11, characterized in that, The cylindrical shell has a loading opening in at least one slot for inserting the reactor vessel into the rotatable conveying cylinder, and an unloading opening for ejecting the reactor vessel from at least one slot in the rotatable conveying cylinder, wherein the loading opening is in the top of the cylindrical shell, and wherein the unloading opening is in the wall of the cylindrical shell.

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