Full-automatic multi-mode immunoassay analyzer

Abstract

The invention belongs to the field of medical inspection automation equipment, and particularly relates to a full-automatic multi-mode immunity analyzer which comprises a frame module, a sample treatment area, a reagent consumable area and a core reaction detection area are arranged on the frame module, the sample treatment area and the reagent consumable area are located on the front portion of the frame module, and the core reaction detection area is located on the front portion of the frame module. The core reaction detection area comprises a magnetic separation module composed of N independent units, a trolley reaction module composed of 2N independent units and a detection module, the 2N independent units of the trolley reaction module are divided into N groups, each group is distributed in an upper layer and a lower layer, and each group is located below each independent unit of the magnetic separation module. The analyzer comprises four trolley reaction modules, two magnetic separation modules, a multi-axis transfer arm and the like, the detection flux is larger than or equal to 100 T / H (four modules are parallel), and the efficiency is improved by 67%. The space utilization rate is improved, the arrangement proportion of the magnetic separator to the trolley reaction module is 1: 2, the magnetic separator and the trolley reaction module are of a vertical nested structure, and the occupied area is reduced by 40%.

Description

Technical Field

[0001] This application belongs to the field of automated medical testing equipment, specifically relating to a fully automated multimodal immunoassay analyzer. Background Technology

[0002] Fully automated immunoassay analyzers are core equipment in clinical testing, quantitatively analyzing biomarkers through antigen-antibody reactions. In recent years, multimodal detection technologies such as chemiluminescence, fluorescence immunochromatography, and flow cytometry have been developed; however, existing equipment still faces significant bottlenecks in integration, automation efficiency, and multimodal collaboration. Key technical issues include: low space utilization due to rotary design in structural layout; time-series conflicts reducing parallel efficiency in multimodal collaboration; the contradiction between single-function and size in POCT adaptation; frequent cup jamming / shutdowns and positioning errors in automation reliability; separate channels and non-reusable samples in multimodal integration; and large sample loading deviations and cross-contamination risks in liquid path accuracy. Summary of the Invention

[0003] To address the aforementioned technical problems in the existing technology, this application proposes a fully automated multimodal immunoassay analyzer that integrates multimodal detection, a highly parallel reaction unit, online consumable replacement, and upgraded liquid circuit control.

[0004] To achieve the above objectives, the technical solution of this application is as follows: A fully automated multimodal immunoassay analyzer includes a frame module, on which a sample processing area, a reagent and consumables area, and a core reaction detection area are respectively arranged. The sample processing area and the reagent and consumables area are located at the front of the frame module. The core reaction detection area includes a magnetic separation module composed of N independent units, a cart reaction module composed of 2N independent units, and a detection module. The 2N independent units of the cart reaction module are divided into N groups, each group is distributed in two layers, and each group is located below each independent unit of the magnetic separation module.

[0005] The detection module includes a chemiluminescence detection module, a flow cytometry fluorescence detection module, and a flow cytometry cell detection module; When performing flow cytometry or flow cell detection, the test liquid is injected into the flow chamber through the sample loading module, and the fluorescence signal is detected by laser excitation. When performing chemiluminescence detection, the reaction module of the cart carrying the reagent strip after the reaction is completed moves to the chemiluminescence detection position for PMT detection. At this time, the PMT is directly aligned with the reaction reagent strip, and the light signal generated by the chemical reaction can be captured without laser excitation.

[0006] Furthermore, the sample processing area includes a sample tube rack with synchronous belt drive, an inverting and mixing module, and a capping module, all fixed on the frame module. The sample processing area is arranged sequentially along the conveying direction of the sample tube rack: the sample tube rack is used to load and transport sample tubes; the inverting and mixing module is located on one side of the conveying path; the capping module grabs the sample tube from a preset position on the sample tube rack and places it into the inverting and mixing module; the inverting and mixing module clamps the sample tube for mixing; the capping module is located after the inverting and mixing module and performs the capping operation on the mixed sample tube; after the sample addition module absorbs the sample, the capping module puts the cap back on the original sample tube and transfers the sample tube to the sample rack.

[0007] Furthermore, the reagent consumable area includes a reagent storage module, a TIP rack module, and a TIP head unloading rack.

[0008] The reagent storage module is a double-layer independent turntable structure, with each turntable driven by an independent stepper motor. The number of reagent positions on the upper turntable is less than that on the lower turntable.

[0009] Furthermore, the trolley reaction module of the core reaction detection area includes a first independent unit, a second independent unit, a third independent unit, and a fourth independent unit, and the magnetic separation module includes a first magnetic separation module and a second magnetic separation module. The first independent unit and the second independent unit are stacked vertically, with the first magnetic separation module positioned above the first independent unit. The third independent unit and the fourth independent unit are stacked vertically, with the second magnetic separation module positioned above the third independent unit. The first magnetic separation module and the second magnetic separation module move up and down through an electric lifting mechanism.

[0010] Furthermore, the bottom of the first independent unit, the second independent unit, the third independent unit, and the fourth independent unit is provided with a temperature-controlled heating plate.

[0011] Furthermore, it also includes a cross-regional operation module, which includes a consumable transfer arm module and a sample dispensing module; The consumable transfer arm module includes a dual-axis linear module, a Z-axis guide rail, and an integrated needle assembly. The integrated needle assembly includes waste liquid needles, substrate liquid needles, and cleaning liquid needles. The consumable transfer arm module is mounted on the frame module via its Y-axis dual-axis linear module. The Z-axis guide rail is mounted on the slide of the Y-axis module. The integrated needle assembly is fixed on the slide of the Z-axis guide rail.

[0012] The sample loading module includes a forearm assembly and a rear arm assembly. The forearm assembly includes a dual-axis linear module and a Z-axis guide rail, while the rear arm assembly includes a linear guide rail and a sample loading needle to aspirate samples into the detection module. This dual-arm assembly is an innovative structure designed to achieve parallel sample processing. The forearm assembly, driven by a dual-axis linear module (covering both the Y and Z axes), is responsible for picking up the pipette tip from the TIP holder module, aspirating the sample from the opened sample tube, and finally loading the sample into the reagent strip in the core reaction area. The rear arm assembly, driven by a linear guide rail (covering both the Y and Z axes), carries a fixed sample loading needle. It is specifically responsible for aspirating the completed sample from the reagent strip and delivering it to the flow chamber of the detection module for flow cytometry and other detection methods. The dual arm assemblies can operate independently and asynchronously, avoiding task conflicts and waiting times between sample dispensing and direct sample loading in a single sample loading module, which is a key design feature for improving overall efficiency.

[0013] Furthermore, it also includes an auxiliary system, which includes a hydraulic system, an HCT module, and a circuit module; The fluid system is connected to the consumable transfer arm module, detection module, sample addition module and HCT module through pipelines. The fluid system adopts a multi-pump collaborative working system, which includes three plunger pumps, one peristaltic pump and two diaphragm pumps. Two plunger pumps are connected via tubing to the cleaning fluid needle and substrate fluid needle of the consumable transfer arm module, respectively. The third plunger pump is connected to the sample loading needle of the rear arm assembly of the sample loading module. The peristaltic pump is connected to the HCT module.

[0014] One diaphragm pump is connected to the waste liquid needle of the consumable transfer arm module to aspirate the chemiluminescence detection waste liquid generated during the reagent strip reaction and cleaning process. The other diaphragm pump is connected to the flow cytometry detection circuit of the detection module to quickly drain the waste liquid after flow cytometry fluorescence and flow cytometry cell detection in the flow chamber and pipeline.

[0015] The HCT module is fixedly located below the moving path of the forearm assembly of the sample dispensing module; The circuit module is connected to all motors, sensors, heating plates, lasers, and pumps / valve via cables.

[0016] The fully automated multimodal immunoassay method includes the following steps: Step 1: Sample loading and recognition; The operator places the sample tubes carrying the samples on the sample tube rack in the sample processing area. The sample tube rack, driven by a synchronous belt, transports the sample tubes to the pre-processing station in sequence. The instrument identifies the sample information through a barcode scanner. Step 2: Mix the sample and open the lid; After the sample tube arrives at the preset position, the capping module grabs the sample tube and places it into the inverting and mixing module. The sample tube is inverted multiple times to be thoroughly mixed. After mixing is complete, the capping module moves above the sample tube to open the cap. The capping module grabs and removes the cap from the sample tube and moves to the preset position to wait. Step 3: HCT detection and precise sampling; The forearm assembly of the sample loading module moves to the TIP holder module and picks up a clean TIP tip; the forearm assembly moves to the opened sample tube and aspirates approximately 100 μL of sample; the forearm assembly carries the sample to the top of the HCT module and, under the control of the fluid system, injects 1 μL of sample for hematocrit detection; the main control board of the circuit module receives the HCT results in real time and calculates the sample dilution ratio required for subsequent tests accordingly; The capping module puts the cap back on the original sample tube and moves the sample tube back to the preset position on the original sample rack. The sample rack then rotates to execute the next cycle. Step 4: Reaction initialization and multimodal assignment; The consumable transfer arm module adds pre-set reagent strips from the turntable of the reagent storage module to the idle unit of the trolley reaction module; Based on the HCT calculation results, the forearm assembly of the sample dispensing module dispenses a precise volume of sample into the sample wells of the reagent strip; simultaneously, the consumable transfer arm module adds a preset reagent from the integrated needle assembly into the reaction wells of the same reagent strip. Step 5: Incubation and asynchronous reaction; The sample and reagents are incubated in designated units of the trolley reaction module, and the temperature-controlled heating plate at the bottom of each independent unit maintains a constant reaction temperature. The 2N independent reaction units are in an asynchronous control state, and the temperature control board of the circuit module is responsible for closed-loop control of the temperature of each unit.

[0017] Step 6: Magnetic separation and cleaning; After incubation, when the magnetic microspheres are separated and cleaned, the magnetic separation module receives a command and descends to a position that fits against the reaction module of the trolley to adsorb the magnetic microspheres; under magnetic adsorption, the waste liquid needle of the consumable transfer arm module absorbs and discards the reaction waste liquid. Subsequently, the cleaning fluid is injected into the cleaning fluid needle of the consumable transfer arm, and the waste fluid needle draws away the waste fluid again, completing the cleaning step. After completion, the magnetic separation module rises and leaves. Step 7: Signal detection and multimodal multiplexing; For chemiluminescence detection: After cleaning, the substrate liquid needle of the consumable transfer arm module adds chemiluminescence substrate to the reaction cup, and the reaction module of the trolley carrying the reaction cup moves to the chemiluminescence detection position, where the PMT in the detection module directly captures the luminescence signal. For flow cytometry / flow cytometry cell detection: the back arm of the sample loading module uses its sample loading needle to draw the reaction solution into the flow chamber of the detection module, where it is excited by a 488nm / 638nm laser, and the resulting fluorescence signal is captured by a silicon photomultiplier tube. Step 8: Waste disposal and result output; After the test is completed, the sample loading module discards the used TIP head into the TIP head unloading rack, and the magnetic separation module pushes the discarded reagent strip into the waste bin; the main control board of the circuit module processes, analyzes and calculates the raw data collected by the test module, and finally generates and outputs the test report.

[0018] The advantages of this application are: 1. The analyzer of this application (including 4 carriage reaction modules, 2 magnetic separation modules, multi-axis transfer arm, etc.) achieves a detection throughput of ≥100T / H (four modules in parallel), with an efficiency improvement of 67%.

[0019] 2. This application improves space utilization. The ratio of the magnetic separator to the trolley reaction module is 1:2, and it is a vertical nested structure, which reduces the floor space by 40%.

[0020] 3. Asynchronous control of 4 independent reaction units: The first to fourth independent units can process different items in parallel (e.g., when the first independent unit performs chemiluminescence, the second independent unit performs flow cytometry analysis at the same time).

[0021] 4. Multimodal sample reuse: Single sample loss ≤ 50 μL.

[0022] 5. The sample loading module works in tandem with the HCT module: HCT detection consumes only 1μL and reuses the sample loading tip, enabling micro-volume detection and streamlined processes. Through unique structural settings and process design, it achieves micro-volume detection and hardware integration of HCT detection, with its core being the "one aspiration, multiple expulsions" working mode.

[0023] 6. Path Planning and Collaborative Positioning: The HCT module is fixedly installed directly below the movement path of the sample dispensing module from the sample tube rack to the core reaction area. This is a precisely calculated positioning that ensures the sample dispensing module can complete the HCT detection without taking a detour when performing its main task. The instrument's main control software schedules the movement trajectory of the sample dispensing module, so that after completing sample aspiration, it automatically passes above the HCT module and performs the sample dispensing operation.

[0024] 7. Achieved precise fluid control with one suction and multiple discharges: One of the aspirations refers to the sample loading module using its TIP head to draw a sufficient amount of sample from the sample tube at once. This sample volume simultaneously meets the sample loading requirements of HCT detection and multiple subsequent cart reaction modules.

[0025] Multi-row HCT sample injection: The sample loading module moves to the top of the HCT module inlet and is driven by a high-precision liquid circuit system to push out a tiny amount of sample (1μL) into the detection cell of the HCT module.

[0026] Multi-row reaction sample loading: After HCT injection is completed, the sample loading module continues to move above the reagent strips of the trolley reaction module and distributes the remaining sample in the TIP head into one or more reaction wells of the reagent strips as needed. Attached Figure Description

[0027] Figure 1 This is a three-dimensional schematic diagram of this application.

[0028] Figure 2 This is a top view of this application.

[0029] Figure 3 This is a rear view diagram of this application.

[0030] Figure 4 This is a schematic diagram of the magnetic separator and the trolley reaction module of this application.

[0031] Figure 5 This is a schematic diagram of the inverted mixing module structure of this application.

[0032] Figure 6 This is a schematic diagram of the reagent storage module structure of this application.

[0033] Figure 7 This is a schematic diagram of the opening module structure of this application.

[0034] Figure 8 This is a schematic diagram of the consumable transfer arm module structure of this application.

[0035] Figure 9 This is a schematic diagram of the sample addition module structure for this application.

[0036] Figure 10 This is a side view of the present application.

[0037] In the attached image: 101-Frame module, 102-Sample tube rack, 103-Inverting and mixing module, 104-Capping module, 105-Reagent storage module, 106-TIP rack module, 107-TIP head unloading rack, 108-Cart reaction module, 109-Magnetic separation module, 110-Detection module, 111-Consumable transfer arm module, 112-Sample addition module, 113-Liquid system, 114-HCT module, 115-Circuit module, 116-Waste bin, 117-Chemiluminescence detection module, 108a-First independent unit, 108b-Second independent unit, 108c-Third independent unit, 108d-Fourth independent unit, 109a-First magnetic separation module, 109b-Second magnetic separation module, 111a-Waste liquid needle, 111b-Substrate liquid needle, 111c-Washing liquid needle. Detailed Implementation

[0038] To make the objectives, technical solutions, and advantages of the embodiments of the invention clearer, the technical solutions of the embodiments of the invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the invention, not all embodiments. The components of the embodiments of the invention described and shown in the accompanying drawings can generally be arranged and designed in various different configurations.

[0039] Therefore, the following detailed description of the embodiments of the invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the invention without inventive effort are within the scope of protection of the invention.

[0040] It should be noted that similar labels and letters in the following figures indicate similar items. Therefore, once an item is defined in one figure, it does not need to be further defined and explained in subsequent figures.

[0041] In the description of this invention, it should be noted that the terms "upper," "vertical," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, or the orientation or positional relationship commonly used when the product of this invention is in use, or the orientation or positional relationship commonly understood by those skilled in the art. They are only used for the convenience of describing this invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a predetermined orientation, or be constructed and operated in a predetermined orientation. Therefore, they should not be construed as limitations on this invention. In addition, the terms "first," "second," etc., are only used to distinguish descriptions and should not be construed as indicating or implying relative importance.

[0042] This invention presents an aircraft surface feature segmentation method based on contour constraint optimization, which uses a deep learning network to segment targets in an image. The method learns feature information from the image through a feature extraction backbone network, then fits the outer contour constraint of the target based on this feature information, initially segmenting the target in the image. Finally, the target contour constraint is used to optimize the segmentation result, achieving high-precision segmentation of each target instance in the image.

[0043] Example 1 A fully automated multimodal immunoassay analyzer includes a frame module 101, on which a sample processing area, a reagent and consumables area, and a core reaction detection area are respectively arranged. The sample processing area and the reagent and consumables area are located at the front of the frame module 101 for easy placement and removal of samples by operators. The core reaction detection area is located at the rear of the frame module 101. The two areas are arranged linearly and connected by a cross-area operation module to achieve the shortest material transport path and the highest operating efficiency. The core reaction detection area includes a magnetic separation module 109 composed of N independent units, a cart reaction module 108 composed of 2N independent units, and a detection module 110. The number of independent units in the cart reaction module 108 and the magnetic separation module 109 can be increased or decreased according to the actual throughput requirements, but it is necessary to ensure that two independent units of the cart reaction module 108 correspond to one independent unit of the magnetic separation module 109. This setting can maximize space utilization and detection parallelism while ensuring magnetic separation efficiency. The 2N independent units of the vehicle reaction module 108 are divided into N groups, each group is distributed in two layers, and each group is located below each independent unit of the magnetic separation module 109.

[0044] The detection module 110 includes a chemiluminescence detection module, a flow cytometry detection module (including a 488nm / 638nm laser and a flow cell), and a flow cytometry cell detection module. While lasers and flow chambers are existing technologies, it is innovative to combine them with different detection reaction reagent strips and signal processing strategies through a pre-designed optical and liquid path, so as to seamlessly realize three detection modes on a single device.

[0045] The core of the detection module 110 is a multimodal flow cytometry detection unit, which includes two fixed lasers at 488nm and 638nm, a flow chamber, and a high-sensitivity photomultiplier tube (PMT) detector.

[0046] When performing flow cytometry or flow cytometry, the test solution is injected into the flow chamber through the sample loading module, where it is excited by a laser and the fluorescence signal is detected. When performing chemiluminescence detection, the reaction module on the cart carrying the completed reagent strip moves to the chemiluminescence detection position for PMT detection. At this time, the PMT is directly aligned with the reaction reagent strip, capturing the light signal generated by the chemical reaction without laser excitation. Through this integrated design of the cart reaction module moving to the flow cytometry sample loading module and then transporting the solution to the detection module via a liquid path, along with the flow path / detection position switching, this invention achieves three detection modes with simplified hardware, significantly reducing instrument complexity and cost.

[0047] Example 2 A fully automated multimodal immunoassay analyzer includes a frame module 101, on which a sample processing area, a reagent and consumables area, and a core reaction detection area are respectively arranged. The sample processing area and the reagent and consumables area are located at the front of the frame module 101 for easy placement and removal of samples by operators. The core reaction detection area is located at the rear of the frame module 101. The two areas are arranged linearly and connected by a cross-area operation module to achieve the shortest material transport path and the highest operating efficiency. The core reaction detection area includes a magnetic separation module 109 composed of N independent units, a cart reaction module 108 composed of 2N independent units, and a detection module 110. The number of independent units in the cart reaction module 108 and the magnetic separation module 109 can be increased or decreased according to the actual throughput requirements, but it is necessary to ensure that two independent units of the cart reaction module 108 correspond to one independent unit of the magnetic separation module 109. This setting can maximize space utilization and detection parallelism while ensuring magnetic separation efficiency. The 2N independent units of the vehicle reaction module 108 are divided into N groups, each group is distributed in two layers, and each group is located below each independent unit of the magnetic separation module 109.

[0048] Detection module 110 includes a chemiluminescence detection module, a flow cytometry detection module (including a 488nm / 638nm laser and a flow cell), and a flow cytometry cell detection module; While lasers and flow chambers are existing technologies, it is innovative to combine them with different detection reaction reagent strips and signal processing strategies through a pre-designed optical and liquid path, so as to seamlessly realize three detection modes on a single device.

[0049] The core of the detection module 110 is a multimodal flow cytometry detection unit, which includes two fixed lasers at 488nm and 638nm, a flow chamber, and a high-sensitivity photomultiplier tube (PMT) detector.

[0050] When performing flow cytometry or flow cytometry, the test solution is injected into the flow chamber through the sample loading module, where it is excited by a laser and the fluorescence signal is detected. When performing chemiluminescence detection, the reaction module on the cart carrying the completed reagent strip moves to the chemiluminescence detection position for PMT detection. At this time, the PMT is directly aligned with the reaction reagent strip, capturing the light signal generated by the chemical reaction without laser excitation. Through this integrated design of the cart reaction module moving to the flow cytometry sample loading module and then transporting the solution to the detection module via a liquid path, along with the flow path / detection position switching, this invention achieves three detection modes with simplified hardware, significantly reducing instrument complexity and cost.

[0051] The sample processing area includes a sample tube rack 102 driven by a synchronous belt, an inverting and mixing module 103, and a capping module 104, all fixed on the frame module 101. The sample processing area is arranged sequentially along the conveying direction of the sample tube rack 102: the sample tube rack 102 is used to load and transport sample tubes; the inverting and mixing module 103 is located on one side of the conveying path; the capping module 104 grabs the sample tube from a preset position on the sample tube rack 102 and places it into the inverting and mixing module 103; the inverting and mixing module 103 clamps the sample tube for mixing; the capping module 104 is located after the inverting and mixing module 103 and performs the capping operation on the mixed sample tube; after the sample addition module 112 absorbs the sample, the capping module 104 puts the cap back on the original sample tube and transfers the sample tube to the sample rack.

[0052] The reagent and consumables area includes a reagent storage module 105, a TIP rack module 106, and a TIP tip unloading rack 107, arranged side-by-side on two parallel straight lines, within the movement coverage of the sample application module 112 and the consumables transfer arm module 111. The reagent storage module 105 is used to store reagents; the TIP rack module 106 is used to load clean pipette tips; and the TIP tip unloading rack 107 is used to unload used pipette tips into the waste bin.

[0053] The reagent storage module 105 has a dual-layer independent turntable structure. Each turntable is driven by an independent stepper motor and can rotate and be positioned independently, so that the transfer extraction head of the consumable transfer arm module 111 can accurately extract the reagent strip from the dispensing port. The upper turntable has fewer reagent positions than the lower turntable. For example, the upper turntable has 6 reagent positions and a dispensing port, while the lower turntable has 7 reagent positions. The TIP rack module 106 is equipped with 96 pipette tips.

[0054] The trolley reaction module 108 in the core reaction detection area includes a first independent unit 108a, a second independent unit 108b, a third independent unit 108c, and a fourth independent unit 108d. The magnetic separation module 109 includes a first magnetic separation module 109a and a second magnetic separation module 109b. The first independent unit 108a and the second independent unit 108b are placed vertically overlapping each other, with the first magnetic separation module 109a positioned above the first independent unit 108a. The third independent unit 108c and the fourth independent unit 108d are placed vertically overlapping each other, with the second magnetic separation module 109b positioned above the third independent unit 108c. The first magnetic separation module 109a and the second magnetic separation module 109b move up and down via an electric lifting mechanism.

[0055] Specifically, the first independent unit 108a and the second independent unit 108b are placed vertically overlapping each other, corresponding to the first magnetic separation module 109a above; the third independent unit 108c and the fourth independent unit 108d are placed vertically overlapping each other, corresponding to the second magnetic separation module 109b above. When magnetic separation is required on a lower reaction unit (such as the second independent unit 108b or the fourth independent unit 108d), the corresponding magnetic separation module will descend to a position closely attached to that lower reaction unit, and its built-in magnetic rod will adsorb and fix the magnetic microspheres in the reaction reagent strip. The strong magnetic field generated by the magnet will penetrate the wall of the magnetic rod and adsorb the magnetic microspheres therein, completing the magnetic separation. After the operation is completed, the magnetic separation module rises back to its original position, preparing for the next operation.

[0056] The magnetic separation module has a vertical lifting function. The first magnetic separation module 109a and the second magnetic separation module 109b both integrate an independent electric lifting mechanism. The electric lifting mechanism can be an existing electric mechanism that can achieve lifting, such as a lead screw driven by a stepper motor.

[0057] The vertical nesting layout of two independent units of the trolley reaction module 108 corresponding to one independent unit of the magnetic separation module 109 is key to achieving high space utilization and is also an important foundation for supporting the instrument's high throughput capability. Temperature-controlled heating plates are installed at the bottom of the first independent unit 108a, the second independent unit 108b, the third independent unit 108c, and the fourth independent unit 108d. These plates are used for precise temperature control of the reaction chamber, achieving closed-loop control with an error of ±0.3℃ through temperature sensors.

[0058] The vehicle reaction module 108 and the magnetic separation module 109 are arranged in a vertical nested structure; Four independent reaction units are controlled asynchronously: the first independent unit 108a, the second independent unit 108b, the third independent unit 108c, and the fourth independent unit 108d can process different items in parallel (e.g., when the first independent unit 108a performs chemiluminescence, the second independent unit 108b simultaneously performs flow cytometry analysis). Chemiluminescence detection module 117: The PMT directly captures the luminescence signal (without excitation light). When the upper and lower layers react simultaneously, each of them can move independently to the preset test position of the PMT without affecting the reaction of the other carriage module.

[0059] Example 3 Based on Embodiment 1 or Embodiment 2, the analyzer also includes a cross-region operation module, which includes a consumable transfer arm module 111 and a sample dispensing module 112; The consumable transfer arm module 111 includes a dual-axis linear module, a Z-axis guide rail (covering the Y-axis / Z-axis), and an integrated needle assembly. The integrated needle assembly includes a waste liquid needle 111a, a substrate liquid needle 111b, and a cleaning liquid needle 111c. The consumable transfer arm module 111 is mounted on a support plate on the base plate of the frame module 101 via its dual-axis linear module (front and rear) along the Y-axis, allowing its movement range to span the reagent consumable area and the core reaction detection area. The Z-axis guide rail is mounted on the slide of the Y-axis module, enabling vertical lifting and lowering movement. The integrated needle assembly (waste liquid needle, substrate liquid needle, and cleaning liquid needle) is fixed on the slide of the Z-axis guide rail. Through the coordinated movement of the Y-axis and Z-axis, precise addition of reagents, substrates, and cleaning liquids, as well as waste liquid extraction, are achieved.

[0060] The sample loading module 112 includes a forearm group and a rear arm group. The forearm group includes a dual-axis linear module and a Z-axis guide rail (for loading the tip to aspirate the sample and loading it onto the reagent strip). The rear arm group includes a linear guide rail (covering the Y-axis / Z-axis) and a sample loading needle to aspirate the sample onto the detection module. This dual-arm group is an innovative structure designed to achieve parallel sample processing. The forearm group is driven by a dual-axis linear module (covering the Y-axis / Z-axis) and is responsible for picking up the tip from the tip holder module 106, aspirating the sample from the opened sample tube, and finally loading the sample onto the reagent strip in the core reaction area. The rear arm group is driven by a linear guide rail (covering the Y-axis / Z-axis) and carries a fixed sample loading needle. It is specifically responsible for aspirating the sample from the reagent strip after the reaction is completed and delivering it to the flow chamber of the detection module 110 for flow cytometry and other detection methods. The dual arm groups can operate independently and asynchronously, avoiding task conflicts and waiting time between sample dispensing and direct sample loading in a single sample loading module, which is a key design feature for improving overall efficiency.

[0061] Example 4 Based on Embodiment 1, Embodiment 2 or Embodiment 3, the analyzer also includes an auxiliary system, which includes a liquid circuit system 113, an HCT module 114 and a circuit module 115; The liquid circuit system 113 is connected to the consumable transfer arm module 111, the detection module 110, the sample addition module 112 and the HCT module 114 through pipelines. The liquid circuit system 113 adopts a multi-pump collaborative working system, which includes three plunger pumps, one peristaltic pump and two diaphragm pumps. Plunger Pumps (High-Precision Metering and Sampling): Application and Connection: The three plunger pumps have distinct functions, all used in active sampling processes requiring extremely high precision. Two of the plunger pumps are connected to the cleaning solution needle 111c and substrate solution needle 111b of the consumable transfer arm module 111 via tubing, specifically responsible for precisely injecting the cleaning solution and chemiluminescent substrate into the reaction reagent strip. The third plunger pump is connected to the sample loading needle of the rear arm assembly of the sampling module 112, specifically responsible for precisely and quantitatively delivering the reacted sample to the flow chamber of the detection module 110 during flow cytometry / flow cytometry cell detection. Plunger pumps offer extremely high liquid metering accuracy (down to 0.1 μL) and excellent repeatability. The added volumes of cleaning solution and substrate directly affect the reaction cleaning effect and the intensity and stability of the chemiluminescence signal; the sample loading rate and volume in flow cytometry directly affect signal resolution and detection accuracy. Therefore, using plunger pumps in these core processes is crucial for ensuring the accuracy and repeatability of detection results.

[0062] The peristaltic pump (contamination-resistant fluid circulation) is connected to the HCT module 114 and is responsible for its complete internal fluid circulation.

[0063] The peristaltic pump features replaceable tubing and a completely isolated pump body. This feature makes it an excellent choice for processing blood samples and preventing cross-contamination. It reliably delivers trace amounts of sample from the sample pool to the testing chamber and then empties the waste blood sample and washing solution from the chamber. It is easy to maintain and cost-effective, perfectly meeting the high-frequency, high-contamination-proof pretreatment requirements of the HCT module.

[0064] Diaphragm pump (for high-flow waste liquid discharge): Application and Connection: Two diaphragm pumps are responsible for the rapid suction of waste liquid in different areas.

[0065] One diaphragm pump is connected to the waste liquid needle 111a of the consumable transfer arm module 111 to aspirate the chemiluminescence detection waste liquid generated during the reaction and cleaning of the reagent strips. The other diaphragm pump is connected to the flow cytometry detection liquid path of the detection module 110 to quickly drain the waste liquid after flow cytometry fluorescence and flow cytometry cell detection in the flow chamber and pipeline.

[0066] The primary requirement for wastewater discharge is speed and thoroughness; instantaneous accuracy is not critical. Diaphragm pumps, with their large flow rate, strong self-priming capability, and ability to operate dry, can efficiently complete wastewater removal tasks. Using two independent diaphragm pumps to handle wastewater from different detection modes further reduces the risk of cross-contamination between different modules in the physical flow path.

[0067] This application innovatively employs a multi-pump collaborative system consisting of three plunger pumps, one peristaltic pump, and two diaphragm pumps, along with a precision solenoid valve assembly, to achieve high-precision, cross-contamination-free transport of liquids across scales from microliters (μL) to milliliters (mL), thereby meeting the differentiated fluid handling requirements of multimodal detection methods such as chemiluminescence, flow cytometry, and flow cytometry.

[0068] The HCT module 114 is fixedly located below the moving path of the forearm assembly of the sample dispensing module 112. It innovatively reuses the sample already aspirated by the sample dispensing module and the TIP head, injecting 1 μL of sample for detection via a precision plunger pump, greatly reducing sample consumption. The sample dispensing module 112 aspirates 100 μL of sample to the TIP head, moves it directly above the HCT module 114, and the TIP head injects 1 μL into the HCT module. The main control board calculates the dilution ratio based on the HCT value, and the liquid circuit system 113 drives the plunger pump to inject the diluent. The circuit module 115 is connected to all motors, sensors, heating plates, lasers and pumps via cables, providing power and control signals.

[0069] Example 5 A fully automated multimodal immunoassay method includes the following steps: Step 1: Sample loading and recognition; The operator places the sample tubes carrying the samples on the sample tube rack 102 in the sample processing area. The sample tube rack 102, driven by a synchronous belt, transports the sample tubes to the pre-processing station in sequence. The instrument identifies the sample information through a barcode scanner. Step 2: Mix the sample and open the lid; After the sample tube arrives at the preset position, the cap opening module 104 grabs the sample tube and places it into the inverting and mixing module 103. The sample tube is inverted multiple times to be fully mixed. After the mixing is completed, the cap opening module 104 moves to the top of the sample tube to open the cap. The cap opening module 104 grabs and removes the cap of the sample tube and moves to the preset position to wait. Step 3: HCT detection and precise sampling; The forearm assembly of the sample loading module 112 moves to the TIP holder module 106 and picks up a clean TIP tip; the forearm assembly moves to the opened sample tube and aspirates approximately 100 μL of sample; the forearm assembly carrying the sample moves above the HCT module 114, and, under the control of the fluid system, injects 1 μL of sample for hematocrit detection; the main control board of the circuit module 115 receives the HCT results in real time and calculates the sample dilution ratio required for subsequent tests accordingly; Module Collaboration: This step innovatively achieves collaboration between the sample loading module, the HCT module, and the liquid circuit system 113, completing the pretreatment detection with extremely low sample consumption (1 μL). The capping module 104 replaces the cap on the original sample tube and moves the sample tube back to the preset position on the original sample rack. The sample rack rotates to execute the next cycle. Step 4: Reaction initialization and multimodal assignment; The consumable transfer arm module 111 adds the pre-set reagent strips from the turntable of the reagent storage module 105 to the idle unit of the trolley reaction module 108; Based on the HCT calculation results, the forearm assembly of the sample dispensing module 112 dispenses a precise volume of sample into the sample wells of the reagent strip; simultaneously, the consumable transfer arm module 111 adds preset reagents from the integrated needle assembly (waste liquid needle, substrate liquid needle, and cleaning liquid needle) into the reaction wells of the same reagent strip. Step 5: Incubation and asynchronous reaction; The sample and reagents are incubated in designated units (such as the first independent unit 108a, the second independent unit 108b, the third independent unit 108c and the fourth independent unit 108d) of the trolley reaction module 108, and the temperature-controlled heating plate at the bottom of each independent unit maintains a constant reaction temperature. The 2N independent reaction units are in an asynchronous control state. For example, while the first independent unit 108a is incubating for a chemiluminescence reaction, the second independent unit 108b may be performing a fluorescence immunochromatography reaction, and the third independent unit 108c may have just finished adding samples and started incubation. The temperature control board of the circuit module 115 is responsible for closed-loop control of the temperature of each unit.

[0070] Step 6: Magnetic separation and cleaning; After incubation, when the magnetic microspheres are separated and cleaned, the magnetic separation module 109 receives an instruction and descends to a position that is in contact with the reaction module 108 of the trolley to adsorb the magnetic microspheres; under magnetic adsorption, the waste liquid needle of the consumable transfer arm module 111 absorbs and discards the reaction waste liquid. Subsequently, cleaning fluid is injected into the cleaning fluid needle of the consumable transfer arm, and the waste fluid needle aspirates the waste fluid again, completing the cleaning step. This process can be repeated multiple times. After completion, the magnetic separation module 109 rises and leaves. This step is the core embodiment of the value of the vertical nested structure. A magnetic separation module serves the upper and lower reaction units through lifting and lowering, realizing efficient resource sharing.

[0071] Step 7: Signal detection and multimodal multiplexing; For chemiluminescence detection: After cleaning, the substrate liquid needle of the consumable transfer arm module 111 adds chemiluminescence substrate to the reaction cup, and the trolley reaction module 108 carrying the reaction cup moves to the chemiluminescence detection position, and the PMT in the detection module 110 directly captures the luminescence signal. For flow cytometry / flow cytometry cell detection: the rear arm assembly of the sample loading module 112 uses its sample loading needle to draw the reaction solution into the flow chamber of the detection module 110, where it is excited by a 488nm / 638nm laser, and the resulting fluorescence signal is captured by a silicon photomultiplier tube. This step demonstrates the asynchronous operation of the dual transfer arms (consumable transfer arm module 111 & sample loading module 112) and multimodal sample reuse (a single sample can be used for multiple detections simultaneously), which greatly improves efficiency.

[0072] This step is crucial for multimodal detection integration, enabling three different detection functions with streamlined hardware by sharing a laser, flow cell, and silicon photomultiplier tube detector.

[0073] Step 8: Waste disposal and result output; After the test is completed, the sample loading module 112 discards the used TIP head to the TIP head unloading rack 107, and the magnetic separation module 109 pushes the discarded reagent strip into the waste bin 116; the main control board of the circuit module 115 processes, analyzes and calculates the raw data collected by the detection module 110, and finally generates and outputs the test report.

[0074] Once the entire machine completes one testing cycle, each module resets or prepares to receive the next sample, achieving continuous, fully automated operation. The entire process, from sample input to result output, highlights the core technological advantages of this invention in parallel processing (asynchronous control), space utilization (vertical nesting), and functional integration (multimodal reuse). Example 6 Basic workflow: Consumable transfer arm module 111 adds reagent strips to each cart reaction module. Sample tube rack 102 transports sample to the mixing position → opening module 104 grabs the sample → inverts and mixes → opening module 104 opens the cap; sample addition module aspirates the sample → distributes it to the trolley reaction module (first independent unit 108a-fourth independent unit 108d). Consumables transfer arm module 111 simultaneously adds reagents / cleaning solution; The magnetic separation module 109 captures and transfers magnetic particles to the sample wells on the reagent strip → the detection module 110 excites fluorescence signals with dual lasers; Discarded TIP heads / waste reagent strips are disposed of in waste bin 116.

[0075] Example 7 Compact POCT implementation plan (volume ≤ 0.1m³) Simplified structural design Reagent storage module 105: Single-layer 8 reagent slots; The vehicle reaction module 108 consists of two units (first independent unit 108a / second independent unit 108b stacked together) + one magnetic separation module (first magnetic separation module 109a). Consumables transfer arm module 111: Dual-axis module (Y-axis travel shortened to 150mm).

[0076] Sample loading module 112: Linear module (Y-axis travel shortened to 150mm).

Claims

1. A fully automated multimodal immunoassay analyzer, characterized in that: The system includes a frame module (101), on which a sample processing area, a reagent and consumable area, and a core reaction detection area are respectively provided. The sample processing area and the reagent and consumable area are located at the front of the frame module (101), and the core reaction detection area is located at the rear of the frame module (101). The core reaction detection area includes a magnetic separation module (109) composed of N independent units, a cart reaction module (108) composed of 2N independent units, and a detection module (110). The 2N independent units of the cart reaction module (108) are divided into N groups, each group is distributed in two layers, and each group is located below each independent unit of the magnetic separation module (109).

2. The fully automated multimodal immunoassay analyzer according to claim 1, characterized in that: The detection module (110) includes a chemiluminescence detection module (117), a flow cytometry fluorescence detection module (110), and a flow cytometry cell detection module (110). When performing flow cytometry fluorescence or flow cytometry cell detection, the test liquid is injected into the flow chamber through the sample loading module (112), and the fluorescence signal is excited by the laser and detected. When performing chemiluminescence detection, the reaction module (108) of the cart carrying the reagent strip after the reaction is completed moves to the chemiluminescence detection position for PMT detection. At this time, the PMT is directly aligned with the reaction reagent strip, and the light signal generated by the chemical reaction can be captured without laser excitation.

3. The fully automated multimodal immunoassay analyzer according to claim 1, characterized in that: The sample processing area includes a sample tube rack (102) driven by a synchronous belt, an inverting and mixing module (103), and a capping module (104), all fixed on the frame module (101). The sample processing area is arranged sequentially along the conveying direction of the sample tube rack (102): the sample tube rack (102) is used to load and transport sample tubes, the inverting and mixing module (103) is located on one side of the conveying path, the capping module (104) grabs the sample tube from the preset position of the sample tube rack (102) to the inverting and mixing module (103), the inverting and mixing module (103) clamps the sample tube for mixing, the capping module (104) is located after the inverting and mixing module (103), and performs the capping operation on the mixed sample tube. After the sample addition module (112) absorbs the sample, the capping module (104) puts the cap back on the original sample tube and transfers the sample tube to the sample rack.

4. The fully automated multimodal immunoassay analyzer according to claim 1, characterized in that: The reagent consumable area includes a reagent storage module (105), a TIP rack module (106), and a TIP head unloading rack (107). The reagent storage module (105) is a double-layer independent turntable structure, with each turntable driven by an independent stepper motor. The number of reagent positions on the upper turntable is less than the number of reagent positions on the lower turntable.

5. The fully automated multimodal immunoassay analyzer according to claim 1, characterized in that: The trolley reaction module (108) of the core reaction detection area includes a first independent unit (108a), a second independent unit (108b), a third independent unit (108c), and a fourth independent unit (108d). The magnetic separation module (109) includes a first magnetic separation module (109a) and a second magnetic separation module (109b). The first independent unit (108a) and the second independent unit (108b) are placed vertically overlapping each other, with the first magnetic separation module (109a) positioned above the first independent unit (108a). The third independent unit (108c) and the fourth independent unit (108d) are placed vertically overlapping each other, with the second magnetic separation module (109b) positioned above the third independent unit (108c). The first magnetic separation module (109a) and the second magnetic separation module (109b) move up and down through an electric lifting mechanism.

6. The fully automated multimodal immunoassay analyzer according to claim 5, characterized in that: Temperature-controlled heating plates are provided at the bottom of the first independent unit (108a), the second independent unit (108b), the third independent unit (108c), and the fourth independent unit (108d).

7. The fully automated multimodal immunoassay analyzer according to claim 1, characterized in that: It also includes a cross-regional operation module, which includes a consumable transfer arm module (111) and a sample dispensing module (112). The consumable transfer arm module (111) includes a dual-axis linear module, a Z-axis guide rail, and an integrated needle assembly. The integrated needle assembly includes a waste liquid needle (111a), a substrate liquid needle (111b), and a cleaning liquid needle (111c). The consumable transfer arm module (111) is mounted on the frame module (101) via its dual-axis linear module on the Y-axis. The Z-axis guide rail is mounted on the slide of the Y-axis module, and the integrated needle assembly is fixed on the slide of the Z-axis guide rail. The sample loading module (112) includes a forearm group and a rear arm group. The forearm group includes a dual-axis linear module and a Z-axis guide rail. The rear arm group includes a linear guide rail and a sample loading needle to draw samples into the detection module (110). The forearm group is driven by a set of dual-axis linear modules, and the rear arm group is driven by a set of linear guide rails and carries a sample loading needle. The two arm groups operate independently and asynchronously.

8. The fully automated multimodal immunoassay analyzer according to claim 1, characterized in that: It also includes an auxiliary system, which includes a hydraulic system (113), an HCT module (114), and a circuit module (115). The liquid circuit system (113) is connected to the consumable transfer arm module (111), the detection module (110), the sample addition module (112) and the HCT module (114) through pipelines. The liquid circuit system (113) adopts a multi-pump collaborative working system, which includes three plunger pumps, one peristaltic pump and two diaphragm pumps. The HCT module (114) is fixedly located below the moving path of the forearm assembly of the sample dispensing module (112); The circuit module (115) is connected to all motors, sensors, heating plates, lasers and pumps via cables.

9. The fully automated multimodal immunoassay analyzer according to claim 8, characterized in that: Two plunger pumps are connected to the cleaning fluid needle (111c) and substrate fluid needle (111b) of the consumable transfer arm module (111) via pipelines, respectively, and the third plunger pump is connected to the loading needle of the rear arm assembly of the loading module (112). The peristaltic pump is connected to the HCT module (114); One diaphragm pump is connected to the waste liquid needle (111a) of the consumable transfer arm module (111) to aspirate the chemiluminescence detection waste liquid generated during the reaction and cleaning of the reagent strips. The other diaphragm pump is connected to the flow cytometry detection liquid path of the detection module (110) to quickly drain the waste liquid after flow cytometry fluorescence and flow cytometry cell detection in the flow chamber and pipeline.

10. A fully automated multimodal immunoassay method, comprising the following steps: Step 1. Sample loading and recognition; The operator places the sample tubes carrying the samples on the sample tube rack (102) in the sample processing area. The sample tube rack (102) transports the sample tubes to the pre-processing station in sequence under the synchronous belt drive. The instrument identifies the sample information through a barcode scanner. Step 2. Mix the sample and open the lid; After the sample tube arrives at the preset position, the cap opening module (104) grabs the sample tube to the inverting and mixing module (103). The sample tube is inverted multiple times to be fully mixed. After the mixing is completed, the cap opening module (104) moves to the top of the sample tube to open the cap. The cap opening module (104) grabs and removes the cap of the sample tube and moves to the preset position to wait. Step 3. HCT detection and precise sampling; The forearm assembly of the sample loading module (112) moves to the TIP holder module (106) and picks up a clean TIP head; the forearm assembly moves to the opened sample tube and aspirates the sample; the forearm assembly carries the sample to the HCT module (114) and injects the sample for hematocrit detection under the control of the liquid circuit system (113); the main control board of the circuit module (115) receives the HCT results in real time and calculates the sample dilution ratio required for subsequent detection accordingly; The opening module (104) puts the sample tube cover back on the original sample tube and moves the sample tube back to the original sample rack preset position. The sample rack rotates to execute the next cycle. Step 4. Reaction initialization and multimodal assignment; The consumable transfer arm module (111) adds the pre-set reagent strips from the turntable of the reagent storage module (105) to the idle unit of the trolley reaction module (108); Based on the HCT calculation results, the forearm assembly of the sample dispensing module (112) dispenses a precise volume of sample into the sample well of the reagent strip; simultaneously, the consumable transfer arm module (111) adds a preset reagent from the integrated needle assembly into the reaction well of the same reagent strip; Step 5. Incubation and asynchronous reaction; The sample and reagents are incubated in designated units of the trolley reaction module (108), and the temperature-controlled heating plate at the bottom of each independent unit maintains a constant reaction temperature. 2N independent reaction units are in asynchronous control state, and the temperature control board of circuit module (115) is responsible for closed-loop control of the temperature of each unit; Step 6. Magnetic separation and cleaning; After incubation, when the magnetic microspheres are separated and cleaned, the magnetic separation module (109) receives the instruction and descends to the position that is in contact with the trolley reaction module (108) to adsorb the magnetic microspheres; under magnetic adsorption, the waste liquid needle (111a) of the consumable transfer arm module (111) absorbs and discards the reaction waste liquid. Subsequently, the cleaning fluid needle (111c) of the consumable transfer arm is injected with cleaning fluid, and the waste fluid needle (111a) draws away the waste fluid again to complete the cleaning step. After completion, the magnetic separation module (109) rises and leaves. Step 7. Signal detection and multimodal multiplexing; For chemiluminescence detection, after cleaning, the substrate liquid needle (111b) of the consumable transfer arm module (111) adds chemiluminescent substrate to the reaction cup, and the trolley reaction module (108) carrying the reaction cup moves to the chemiluminescence detection position, and the PMT in the detection module (110) directly captures the luminescence signal. For flow cytometry / flow cytometry cell detection, the back arm assembly of the sample loading module (112) uses its sample loading needle to draw the reaction solution into the flow chamber of the detection module (110), where it is excited by a 488nm / 638nm laser, and the resulting fluorescence signal is captured by a silicon photomultiplier tube. Step 8. Waste treatment and result output; After the test is completed, the sample loading module (112) discards the used TIP head to the TIP head unloading rack (107), and the magnetic separation module (109) pushes the discarded reagent strip into the waste bin (116); the main control board of the circuit module (115) processes, analyzes and calculates the raw data collected by the detection module (110), and finally generates and outputs the test report.

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