A biological sample automated analysis temperature control system and control method

Abstract

The application discloses a kind of biological sample automatic analysis temperature control system and control method, belong to medical instrument technical field.The double temperature control mode analysis system is constructed by integrating reagent carousel, sample carousel / sample tube flow mechanism, reagent dispensing unit, sample dispensing unit, reaction disc and controller;Reagent carousel can be efficiently refrigerated in two ways, using thermoelectric refrigeration and coolant liquid cooling transfer form respectively, the first reagent carousel is provided with a center gear disc to realize uniform suspension of magnetic beads, and the second reagent carousel is provided with an identifier to complete reagent information identification;The controller is used to detect the state of the system, and the reagent carousel is controlled to run at 13-18℃ in detection mode, and the detection mode runs at 2-8℃.The application can improve the initial temperature of the reaction system without significantly changing the hardware, shorten the incubation time, improve the detection efficiency and result accuracy while achieving energy saving effect, and avoid the risk of reagent inactivation and droplet caused by heating of dispensing head.

Description

Technical Field

[0001] This invention belongs to the field of medical device technology, specifically relating to an automated temperature control system and control method for biological sample analysis. Background Technology

[0002] Automated analysis systems for biological samples can perform qualitative or quantitative detection of specific target substances in biological samples using optical, electrical, and imaging methods. The detection results of automated analysis systems have higher reproducibility and faster result acquisition speed, thus becoming an indispensable device in modern medical systems. Currently, photoimmunoassay systems, which are developed from chemiluminescence detection technology and are widely used, can perform highly specific and accurate determination of target protein substances in biological samples by utilizing the binding characteristics of antigens and antibodies.

[0003] To ensure reagent stability, photoimmunoassay systems must keep reagents at a low temperature of 2-8°C for extended periods. However, adding low-temperature reagents to the reaction vessel lowers the initial temperature of the reaction system, requiring the reaction plate to be incubated at a constant temperature for a longer period to reach the optimal reaction temperature for antigen and antibody. This directly results in a significant increase in the total time required for batch sample testing and low testing efficiency.

[0004] Existing technologies have already addressed this inherent technical problem stemming from the underlying design. International application WO2023127878A1 provides a solution by configuring a controllable heating unit at a specific location within the reagent dispensing unit. This heating unit heats a specific area of ​​the dispensing unit, raising the temperature of the absorbed reagent. To achieve greater heat compensation for the reagent, the set temperature of the heating unit is higher than the incubation temperature of the reaction plate, thus improving overall reaction efficiency. However, this solution requires a higher set temperature, potentially causing the reagent to be placed at a higher target temperature, which could lead to heat sensitivity. The failure of highly effective reagent components can affect the accuracy of test results. On the other hand, additional equipment and control methods are required, and the small internal space of the dispensing head can easily lead to local overheating and interface instability, which reduces the reliability of dispensing head pipetting. In order to reduce the impact of overheating and the potential activity of effective components, US Patent 10788479B2 limits the target heating temperature of the heating unit of the dispensing head to 39°C. However, the small internal space of the dispensing head still causes interface instability, which may lead to the risk of reagent dripping during the transfer of reagents during heating, resulting in reduced dispensing accuracy and affecting the accuracy of test results.

[0005] Therefore, there is an urgent need to design a solution without changing the structure of the existing detection system to solve the technical problem of long reaction plate incubation time caused by the reagent turntable operating at a lower target temperature that is conducive to ensuring reagent stability within the shelf life. This solution also needs to overcome the risks of reduced reliability and testing accuracy caused by heating part of the reagent in a confined space in the existing technology. Summary of the Invention

[0006] To address the aforementioned problems in the prior art, the present invention is achieved through the following technical solution: A first aspect of the present invention provides an automated temperature control system for biological sample analysis, comprising: a reagent turntable, a sample relay unit, a reagent dispensing unit, a sample dispensing unit, a reaction tray, and a controller; A reagent turntable is used to hold reagents and can be either a first reagent turntable or a second reagent turntable. The sample relay section is used for placing and transferring samples, and includes a sample turntable or sample tube transfer mechanism; The reaction plate is used to receive samples and reagents for reaction; the reagent dispensing unit is located near the reagent turntable and is used to transfer reagents from the reagent turntable to the reaction plate; the sample dispensing unit is located near the sample relay section and is used to transfer samples from the sample relay section to the reaction plate. The controller is electrically connected to the reagent turntable and is used to detect the current status of the system and control the target operating temperature of the reagent turntable according to the current system status. The controller includes an interactive control unit, which controls the reagent dispensing unit to transfer reagents from the reagent turntable operating at the first target temperature to the reaction plate. When the reagent turntable is operating at the second target temperature, the reagent dispensing unit is controlled not to transfer reagents, and the second target temperature is lower than the first target temperature.

[0007] The reagent turntable is a first reagent turntable, which includes: a first reagent receiving cavity for accommodating reagent tube groups; a first driving mechanism disposed at the bottom of the first reagent receiving cavity for driving the first reagent receiving disk to rotate; the first reagent receiving disk is separately disposed at the upper part of the bottom of the first reagent receiving cavity; the first reagent receiving disk is provided with a plurality of locking areas for locking the reagent tube groups; and a reagent loading port is provided on the side wall of the first reagent receiving cavity for transmitting the reagent tube groups that are introduced into the reagent receiving cavity by the reagent delivery rail. A first refrigeration unit is also attached to the bottom of the first reagent receiving cavity. The first refrigeration unit is used to output cold energy to the first reagent receiving cavity to maintain its internal temperature.

[0008] A central toothed disk is also fixedly installed inside the first reagent receiving cavity. The central toothed disk is separated and installed on the upper part of the first reagent receiving disk. The first reagent receiving disk is also provided with tooth-shaped structures evenly spaced around the circumference of the central toothed disk, which are used to mesh and connect with the bottom tooth-shaped structures of the magnetic bead storage well unit.

[0009] The reagent tube assembly is preferably a spindle-shaped or boat-shaped structure, and the reagent tube assembly is provided with several reagent well units, which are preferably arranged in a straight line.

[0010] The reagent turntable is a second reagent turntable, which includes: a second reagent receiving cavity for accommodating reagent tube groups; a second driving mechanism is disposed at the bottom of the second reagent receiving cavity for driving the rotation of the second reagent receiving turntable; the second reagent receiving turntable is provided with a plurality of reagent slots for securing reagent tube groups; an identification window is provided on the side wall of the second reagent receiving cavity; an identifier is fixedly disposed at a relative position outside the identification window for identifying reagent tube group information passing through the identification window. A second refrigeration unit is also attached to the bottom of the second reagent receiving chamber. The second refrigeration unit is used to output cold energy to the second reagent receiving chamber to maintain its internal temperature. The second refrigeration unit includes a refrigeration section for supplying liquid cooling refrigerant, which carries away waste heat through the refrigerant.

[0011] The first refrigeration unit is preferably a thermoelectric cooler. The cold end of the thermoelectric cooler is attached to the bottom of the first reagent receiving chamber and outputs cooling energy to the first reagent receiving chamber to maintain its internal temperature. The hot end of the thermoelectric cooler is connected to heat dissipation fins and carries away waste heat through convection air. The second refrigeration unit is preferably a refrigerant.

[0012] The reaction tray is also equipped with a heating element, which outputs heat to the reaction tray to adjust the incubation reaction temperature, which is set to 37°C.

[0013] The sample relay unit includes a sample turntable. The reagent turntable and the sample turntable are arranged in a triangle on both sides of the reaction plate. The running trajectories of the reagent dispensing unit and the sample dispensing unit are tangent to different sides of the triangle formed by the reagent turntable, the sample turntable and the reaction plate, so as to avoid the trajectory crossing and causing reagent or sample contamination.

[0014] The controller also includes a control mode decision unit, which controls the reagent turntable to operate at a first target temperature or a second target temperature.

[0015] A second aspect of the present invention provides a control method comprising the following steps: The controller detects the current system status and controls the target operating temperature of the reagent turntable based on the current system status. When the system is currently in sample detection mode, the controller controls the first or second refrigeration unit to make the reagent turntable operate at the first target temperature, which is 13-18℃. When the system is currently in sample testing mode, the controller controls the first or second refrigeration unit to make the reagent turntable operate at the second target temperature, which is 2-8℃.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. This invention constructs a dual-temperature-controlled automated biological sample analysis system by integrating two different types of sample relay units (reagent turntable and sample turntable / sample tube transfer mechanism), reagent dispensing unit, sample dispensing unit, reaction plate, and controller. The reagent turntable is divided into a first reagent turntable and a second reagent turntable, which respectively use thermoelectric cooling and refrigerant cooling to achieve precise temperature control. The first reagent turntable is equipped with a central toothed disk and toothed structure to enable the magnetic beads and reagents to rotate and suspend uniformly. The second reagent turntable is equipped with an identification window and an identifier to complete the automatic identification of reagent tube group information. The system layout adopts a triangular tangential trajectory design to effectively avoid cross-contamination between samples and reagents. It can be used for high-precision detection and analysis of biological samples such as fully automated chemiluminescence immunoassay, and solves the problems of slow incubation, easy contamination, and low reliability of existing equipment from a structural perspective.

[0017] 2. This invention utilizes a built-in dual-mode temperature control logic in the controller. In sample detection mode, the reagent turntable is controlled to operate at a first target temperature of 13–18°C, while in sample waiting mode, it switches to a second target temperature of 2–8°C. This eliminates the need for additional heating components in the dispensing head, thereby increasing the initial temperature of the reaction system and significantly shortening the incubation time. While ensuring reagent stability, it significantly improves the efficiency of batch sample detection, effectively solving the problem of long incubation time and slow detection speed caused by low-temperature reagents.

[0018] 3. This invention does not require modification of the existing detection system hardware structure, avoiding risks such as local overheating, inactivation of thermosensitive reagents, unstable liquid interface, reagent dripping, and decreased dispensing accuracy caused by heating in the confined space of the dispensing head. At the same time, it reduces the complexity of the system structure and control costs, and the consistency and reliability of the detection results are higher, providing a reliable guarantee for the efficient and stable operation of automated biological sample analysis equipment.

[0019] The present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0020] Figure 1 This is a top view of an automated temperature control system for biological sample analysis provided in Embodiment 1 of the present invention; Figure 2 This is a three-dimensional schematic diagram of the first reagent turntable provided in Embodiment 1 of the present invention; Figure 3 This is a cross-sectional view of the first reagent turntable provided in Embodiment 1 of the present invention; Figure 4 This is a three-dimensional layout diagram of an automated biological sample analysis temperature control system provided in Embodiment 1 of the present invention; Figure 5 This is a schematic diagram of a controller provided in Embodiment 1 of the present invention; Figure 6 This is a three-dimensional schematic diagram of the second reagent turntable provided in Embodiment 2 of the present invention; Figure 7 This is a cross-sectional view of the second reagent turntable provided in Embodiment 2 of the present invention; Figure 8 This is a top view of another automated biological sample analysis temperature control system provided in Embodiment 3 of the present invention; Figure 9 This is a three-dimensional layout diagram of another automated biological sample analysis temperature control system provided in Embodiment 3 of the present invention; Figure 10 This is a comparison chart of the detection results of the reagent turntable in two modes of operation and the reagent turntable operating at continuous low temperature in the confidence interval V10; Figure 11 This is a comparison chart of detection results performed at confidence interval V10 when the reagents were stored at different temperatures; Explanation of reference numerals in the attached figures: 10-Reaction tray; 20-Reagent turntable; 30-Sample turntable; 40-Controller; 50-Sample tube transfer mechanism; 51-Sample tube transfer rail; 11-Reaction cup receiving well unit; 21-Reagent tube assembly; 211-Reagent well unit; 31-Sample tube rack; 311-Sample tube receiving well; 200-Reagent dispensing unit; 300-Sample dispensing unit; 41-Sample transport rail; 42-Reagent transport rail; 401-Reagent cleaning unit; 402-Sample cleaning unit; 201-Clamping area; 202 - Central toothed disc; 203 Reagent loading port; 220 First cooling unit; 230 Heat dissipation fins; 240 First drive mechanism; 210 First reagent turntable; 212 First reagent receiving cavity; 222 First reagent receiving plate; 223 Toothed structure; 210' Second reagent turntable; 204 Reagent slot; 205 Second reagent receiving plate; 206 Identification window; 207 Second reagent receiving cavity; 22- Identifier; 250 Second cooling unit; 260 Second drive mechanism. Detailed Implementation

[0021] To further illustrate the technical means and effects adopted by the present invention to achieve the intended purpose, the following detailed description of the solution according to the present invention is provided in conjunction with the accompanying drawings and specific embodiments.

[0022] The foregoing and other technical contents, features, and effects of the present invention will be clearly presented in the following detailed description of specific embodiments in conjunction with the accompanying drawings. Through the description of the specific embodiments, a more in-depth and concrete understanding can be gained of the technical means and effects adopted by the present invention to achieve its intended purpose. However, the accompanying drawings are for reference and illustration only and are not intended to limit the technical solutions of the present invention.

[0023] It should be noted that, in this document, relational terms such as "first" and "second" are used merely to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations are intended to cover non-exclusive inclusion, such that an article or apparatus comprising a list of elements includes not only those elements but also other elements not expressly listed. Without further limitations, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the article or apparatus that includes said element.

[0024] Currently, automated analysis of biological samples is essential for the diagnosis of infectious diseases in organisms. In biological sample detection systems, ex vivo biological samples such as blood, saliva, cerebrospinal fluid, and urine are transferred and dispensed, and specific reactions occur in the incubation reaction plate. This causes changes in the physical properties of the liquid in the reaction plate, such as optical properties, and finally, the analysis results are obtained to quantitatively obtain the detection results of target substances.

[0025] like Figure 1 The figure shown is a top view of an automated biological sample analysis temperature control system provided in Embodiment 1 of the present invention. In this embodiment, the system is equipped with an operating table, on which different functional areas are arranged, including: a reagent turntable 20, a sample turntable 30, a reagent dispensing unit 200, a sample dispensing unit 300, a reaction plate 10, and a controller 40.

[0026] The reaction tray 10 contains multiple reaction cup receiving well units 11 arranged in a ring-shaped distribution. Preferably, four or more distribution rings can be arranged to facilitate rapid batch incubation. Furthermore, the reaction tray 10 is equipped with heating elements to output heat to adjust the incubation reaction temperature, ensuring that the reaction tray 10 can be controlled within a suitable incubation reaction temperature range. The preferred incubation reaction temperature is 37°C.

[0027] A reagent turntable 20 is arranged adjacent to the reaction plate 10, and the reaction plate 10 is arranged in the internal area of ​​the operating table relative to the reagent turntable 20. This ensures that any contamination that may occur during the incubation operation is eliminated in a timely manner, and that the loading of reagents is more convenient.

[0028] The reagent turntable 20 is used to hold reagents and can be either a first reagent turntable 210 or a second reagent turntable 210'. Specifically, as shown... Figure 2The diagram shown is a three-dimensional schematic diagram of the first reagent turntable provided in Embodiment 1 of the present invention. The first reagent turntable 210 includes: a first reagent receiving cavity 212 for accommodating the reagent tube group 21, and a first reagent receiving disk 222 separately disposed on the upper part of the bottom of the first reagent receiving cavity 212. The first reagent receiving disk 222 is provided with a plurality of locking areas 201 for locking the reagent tube group 21.

[0029] The reagent tube assembly 21 can be configured as a whole or as separate units. The overall configuration is preferably a spindle-shaped or boat-shaped structure, containing at least a separable magnetic bead storage well unit. The reagent tube assembly 21 is also provided with a number of reagent well units 211, which are preferably arranged in a straight line. The reagent well unit 211 closest to the center of the first reagent receiving tray 222 is set as a magnetic bead storage well unit. The conveying mechanism transports the reagent tube assembly 21 with various reagents configured to it to the reagent turntable 20 through the reagent conveying rail 42.

[0030] The circumference of the reagent turntable 20 can be divided into dozens of receiving areas, each of which can receive one reagent tube group 21. In this way, the reagent turntable 20 can load dozens of reagent tube groups 21 at one time, which can ensure the detection running time and the efficient and rapid compatibility of the detection system with different detection items. The used reagent tube group 21 can also cooperate with the conveying mechanism and be unloaded from the reagent turntable 20 in a timely manner through the reagent conveying rail 42.

[0031] like Figure 3 The diagram shows a cross-sectional view of the first reagent turntable 210 provided in Embodiment 1 of the present invention. The first reagent receiving cavity 212 is also fixedly provided with a central toothed disk 202, which is separately disposed on the upper part of the first reagent receiving disk 222. In order to ensure that the magnetic bead reagent can be efficiently and fully stirred in the reagent turntable 20 and be in a uniform suspension state, the first reagent receiving disk 222 is also provided with toothed structures 223 evenly distributed around the circumference of the central toothed disk 202, which are used to mesh with the toothed structures at the bottom of the magnetic bead storage well unit. When the first reagent receiving disk 222 rotates, the magnetic bead reagent inside the magnetic bead storage well unit can be driven to generate a rotational motion under the action of the meshing toothed structures 223, thereby enhancing the turbulence of the magnetic bead reagent inside to ensure that the magnetic beads are suspended more uniformly, and ensuring that the magnetic beads in the well unit can always be efficiently and uniformly preserved during the detection process.

[0032] The circumferential sidewall of the first reagent receiving cavity 212 is provided with a reagent loading port 203, which is used to transfer the reagent tube group 21 from the reagent delivery rail 42 into the reagent receiving cavity.

[0033] A first driving mechanism 240 is located at the bottom of the first reagent receiving cavity 212 and is used to drive the rotation of the first reagent receiving disk 222. The first driving mechanism 240 is located below the outside of the first reagent receiving cavity 212. The first driving mechanism 240 is equipped with a rotary drive motor and a position sensor that cooperates with the motor to realize the positioning and drive control of the first reagent receiving disk 222. A first refrigeration unit 220 is also attached to the bottom of the first reagent receiving cavity 212. The first refrigeration unit 220 is used to output cold energy to the first reagent receiving cavity 212 to maintain its internal temperature and is electrically connected to the controller 40. The first refrigeration unit 220 is configured as a thermoelectric cooler. The cold end of the thermoelectric cooler is attached to the bottom of the first reagent receiving cavity 212 and outputs cold energy to the first reagent receiving cavity 212. The hot end of the thermoelectric cooler is connected to the heat dissipation fins 230 to remove waste heat through convection air. Preferably, the thermoelectric cooler is a Peltier cooler.

[0034] The sample turntable 30 is used to place samples. The sample tube rack 31 is radially transferred to the sample turntable 30 by the sample transport rail 41 connected in the circumferential direction. In this embodiment, the sample turntable 30 serves as a sample relay. The sample tube rack 31 is equipped with several sample tube receiving wells 311. In order to ensure that the sample tube rack 31 can hold more sample tubes, the sample tube receiving wells 311 inside the sample tube rack 31 are arranged in a non-linear staggered manner. After the sample tube rack 31 is inserted, the sample tube receiving wells 311 inside are arranged in different radial angle ranges and the receiving wells are arranged in a dislocation type, so that when the sample transport rail 41 transports the sample tube rack 31 to the sample turntable 30, each sample tube can be scanned without obstruction to obtain the associated information.

[0035] The sample turntable 30 and reagent turntable 20 are positioned in the front area of ​​the operating table, with the line connecting their centers parallel to the central axis of the operating table. The reagent turntable 20 and sample turntable 30 are arranged in a triangle at both ends of the reaction plate 10, which is used to receive samples and reagents for reaction. The reagent dispensing unit 200 is positioned adjacent to the reagent turntable 20 and is capable of horizontal rotation and vertical lifting. The reagent dispensing unit 200 is used to cooperate with the reagent turntable 20 to transfer a specific amount of various reagent samples from the sample turntable 30 to the reaction plate 10. The reaction cups in the reaction plate 10 can be made of disposable plastic to reduce the risk of contamination from repeated use.

[0036] like Figure 4The diagram shown is a three-dimensional layout of an automated biological sample analysis temperature control system according to Embodiment 1 of the present invention. A three-dimensional space of a predetermined height is arranged below the operating table. This height ensures that the operator can operate in the most comfortable posture during manual operations, and also allows for the maximum capacity storage of various reagents and cleaning agents from the detection system within the lower space. It also allows for the rational configuration of connecting fluid circuits and electrical components. The preferred height here is 500mm-1100mm. To reduce the risk of contamination during dispensing and pipetting operations, a cleaning unit is also provided on the operating table. Figure 4 The diagram illustrates the reagent cleaning unit 401 of the reagent dispensing unit 200. After several reagent transfers, or when transferring different types of reagents, the dispensing unit moves the dispensing needle to the reagent cleaning unit 401, where it works with the cleaning solution to clean the inside or outside of the dispensing needle. Here, because the running trajectories of the sample dispensing unit 300 and the reagent dispensing unit 200 do not overlap, and the running trajectories of the reagent dispensing unit 200 and the sample dispensing unit 300 are tangent to different sides of the triangle formed by the reagent turntable 20, the sample turntable 30 and the reaction plate 10, the trajectory intersection is avoided, which could cause reagent or sample contamination. Therefore, the two units can be driven to perform sample and reagent dispensing within the overlapping time sequence, ensuring efficient and low-contamination dispensing operation.

[0037] like Figure 5 The diagram shown is a schematic of a controller provided in Embodiment 1 of the present invention. The controller 40 is electrically connected to the reagent turntable 20. The controller 40 is used to detect the current state of the system and control the target operating temperature of the reagent turntable according to the current state of the system.

[0038] Specifically, the controller 40 includes a control mode decision unit and an interactive control unit. The control mode decision unit controls the reagent turntable 20 to operate at a first target temperature or a second target temperature. The interactive control unit interacts with an external operating interface. The interactive control unit can also output control commands for motion functions within the system, such as control commands for the dispensing needle movement. It can generate dispensing needle movement control commands based on the target operating temperature of the reagent turntable 20 output by the control mode decision unit and schedule the dispensing needle operation sequence. The control mode decision unit includes a sensor signal processing unit and a target temperature generation unit. The sensor signal processing unit detects the current system state and includes a cleaning pump current sensor and a module timer. It uses current signals and / or time signals to determine the current system state. The target temperature generation unit can output at least two different target operating temperatures for the reagent turntable 20, used to control the reagent turntable 20 to operate at the target temperature according to the current system state.

[0039] When the automated biological sample analysis system is in sample detection mode, the controller 40 controls the reagent turntable 20 to operate at a first target temperature of 13-18℃; when the automated biological sample analysis system is in sample waiting mode, the controller 40 controls the reagent turntable 20 to operate at a second target temperature of 2-8℃.

[0040] When the system is in sample detection mode, the reagent turntable 20 stores the reagents inside at a higher first target temperature. After the reagent dispensing unit 200 transfers the sample reagents to the reaction plate 10, the overall liquid temperature inside the reaction plate 10 is higher, requiring less heat transfer within the reaction plate 10, which allows the optimal reaction temperature to be reached more quickly. The system hardware is simpler and the cost is lower. It also avoids problems such as dripping caused by heating in the dispensing unit. When the system is in sample testing mode, the reagent turntable 20 stores the reagents inside at a lower second target temperature.

[0041] The interactive control unit is electrically connected to the operator's interactive interface and can control the reagent dispensing unit 200 to transfer reagents from the reagent turntable 20 operating at a first target temperature to the disposable reaction tubes of the reaction tray 10. When the reagent turntable 20 is operating at a second target temperature, the reagent dispensing unit 200 is controlled not to transfer reagents to ensure the reliability of reagent transfer and prevent problems such as execution command conflicts that may occur during system operation.

[0042] The controller 40 can also automatically determine the operating status of the dispensing unit, such as the reagent dispensing unit 200, so that the system has an autonomous control mode. This prevents the detection system from always maintaining the detection module due to the operator forgetting. When the reagent dispensing head does not perform reagent transfer operation within the set interval time, that is, when the time recorded by the module timer exceeds the predetermined time threshold, the controller 40 controls the reagent turntable 20 to run at the second target temperature to preserve the reagent inside. In this way, the detection system can automatically enter the non-detection mode.

[0043] like Figure 6The diagram shown is a three-dimensional schematic of the second reagent turntable provided in Embodiment 2 of the present invention. The second reagent turntable 210' includes: a second reagent receiving cavity 207 for accommodating reagent tube group 21; a second driving mechanism 260 disposed below the cavity of the second reagent receiving cavity 207 for driving the rotation of the second reagent receiving disk 205; the second reagent receiving disk 205 is provided with a plurality of reagent slots 204 for engaging the reagent tube group 21; the reagent tube group 21 can be inserted into the reagent slots 204 fixed on the second reagent receiving disk 205; an identification window 206 is provided on the side wall of the second reagent receiving cavity 207; an identifier 22 is fixedly disposed at a relative position outside the identification window 206, which can preferably be an image barcode identifier; when the second reagent receiving disk 205 is driven by the second driving mechanism 260, it drives the reagent tube group 21 to rotate; a barcode is attached to the end of the reagent tube group 21, so that when the reagent tube group 21 passes through the identification window 206, the information of the reagent tube group 21 is identified.

[0044] like Figure 7 The diagram shows a cross-sectional view of the second reagent turntable provided in Embodiment 2 of the present invention. The second driving mechanism 260 is disposed below the outer surface of the second reagent receiving cavity 207. A second refrigeration unit 250 is also attached to the bottom of the outer surface of the second reagent receiving cavity 207. The second refrigeration unit 250 is used to output cooling energy to the second reagent receiving cavity 207 to maintain its internal temperature. It includes a refrigeration section for supplying liquid cooling refrigerant, which carries away waste heat. The second refrigeration unit 250 is electrically connected to the controller 40. Preferably, the second refrigeration unit can be a whole or multiple units can be attached to the bottom of the outer surface of the second reagent receiving cavity 207 to make the cooling output more uniform.

[0045] like Figure 8 The diagram shows a top view of another automated biological sample analysis temperature control system provided in Embodiment 3 of the present invention. The reagent turntable 20 is the second reagent turntable 210', and the sample turntable 30 is replaced by a sample tube transfer mechanism 50. As another form of sample relay, this makes the sample loading and transfer method more flexible. The sample tube transfer mechanism 50 can realize the transfer of the entire sample tube rack 31 or the transfer of a single sample tube. The sample tube transfer mechanism 50 is located near the rear end of the operating table, adjacent to the reaction tray 10 and the sample dispensing sheet located between them. The reagent turntable 20 is set at the front of the operating table in unit 300. This arrangement makes the loading and unloading of reagents in the system more efficient and convenient. The reagent turntable 20 and the sample tube transfer mechanism 50 are distributed on different sides of the reaction plate 10, so that the sample dispensing unit 300 and the reagent dispensing unit 200 can be configured in a larger non-overlapping area. The movement trajectories of the sample dispensing unit 300 and the reagent dispensing unit 200 do not overlap at all. More preferably, the arc of the sample dispensing unit 300 intersecting the reaction plate 10 is alternated with the arc of the reagent dispensing unit 200 intersecting the reaction plate 10.

[0046] like Figure 9 The diagram shows a three-dimensional layout of another automated biological sample analysis temperature control system provided in Embodiment 3 of the present invention. The sample tube transfer mechanism 50 is equipped with multiple sample tube transfer rails 51. Preferably, there are 3 sample tube transfer rails 51, so that the sample tubes or sample tube racks 31 after sampling can be removed from the detection system from different sample tube transfer rails 51. In order to ensure that the reagent dispensing unit 200 and the sample dispensing unit 300 can perform liquid dispensing and transfer with low risk of contamination, a reagent cleaning unit 401 and a sample cleaning unit 402 are also configured to clean the reagent dispensing unit 200 and the sample dispensing unit 300.

[0047] Embodiment 4 of the present invention provides a control method, comprising the following steps: The controller 40 detects the current status of the system and controls the reagent turntable 20 to run at the target temperature based on the current status of the system.

[0048] When the system is in sample detection mode, the controller 40 controls the first cooling unit 220 or the second cooling unit 250 to make the reagent turntable 20 operate at the first target temperature, which is 13-18℃.

[0049] When the system is currently in sample testing mode, the controller 40 controls the first cooling unit 220 or the second cooling unit 250 to make the reagent turntable 20 operate at the second target temperature, which is 2-8℃.

[0050] The interactive control unit controls the reagent dispensing unit 200 to transfer reagents from the reagent turntable 20, which operates at a first target temperature, to the disposable reaction tubes of the reaction tray 10. When the reagent turntable 20 operates at a second target temperature, the reagent dispensing unit 200 is controlled not to transfer reagents to ensure the reliability of reagent transfer and to prevent problems such as execution command conflicts that may occur during system operation.

[0051] When the system is in sample detection mode, the reagent turntable 20 stores the reagents inside at a higher first target temperature. After the reagent dispensing unit 200 transfers the sample reagents to the reaction plate 10, the overall liquid temperature in the reaction plate 10 is higher, requiring less heat transfer within the reaction plate 10, which allows the system to reach the optimal reaction temperature more quickly. The system hardware is simpler and the cost is lower. By controlling the target temperature differently for the detection period and the waiting period, energy is saved while avoiding problems such as dripping caused by temperature rise in the reagent dispensing unit 200. When the system is in sample waiting mode, the reagent turntable 20 stores the reagents inside at a lower second target temperature.

[0052] Figure 10This is a comparison chart of the detection results of two modes of reagent turntable operation and a reagent turntable operating at continuous low temperature within the confidence interval V10. Here, standard samples with known concentrations of HBV and HCV that are photodetector-free can be selected for detection. Photodetector-free equipment of the same model and batch is used. In one system, the reagent turntable 20 is always operated at a low target temperature of 2-8°C to store the reagents inside. The system in this invention alternates between a high storage temperature of 13-18°C and a low storage temperature of 2-8°C at 12-hour intervals to store the reagents within different target temperatures. The incubation time is configured to be 0.75 to 0.95 times that of the previous equipment. Under the same conditions, for multiple detection items, the detection results of both systems are within the confidence interval V10 of the standard concentration. This indicates that appropriately increasing the reagent storage temperature in the detection mode has little impact on the final detection results. Differentiated target temperature control during the detection period and the waiting period not only makes the system more energy-efficient but also allows for faster and more efficient acquisition of detection results.

[0053] Figure 11 This is a comparison graph of detection results performed at confidence interval V10 when the reagent is stored at different temperatures. It is known that the reagent will denature at certain high temperatures, which will affect the detection results. Therefore, the reagent turntable 20 is kept constant at different target temperatures and tested at intervals over a relatively long period of time. Here, t10 is the time point at which the temperature affects the test results after long-term storage, and the subsequent time intervals are the same. The comparison chart of the test results shows that the storage temperatures outside the 5-16℃ range of the two target temperature differences of the present invention include two temperatures: 25℃ and 30℃. The incubation time of the reaction plate 10 of the experimental equipment is configured to be the same. After a certain period of time, the high temperature will have an irreversible effect on the activity of the reagent, causing the test results to deviate from the confidence interval V10. However, the test results within the target temperature range are always within the confidence interval V10 of the test results of the target substance with known concentration. As the temperature increases, the deviation from the confidence interval V10 becomes further. However, if the temperature difference is too small, it will not be able to meet the requirement that the reagent in the reagent turntable has a sufficient compensation temperature, resulting in a small improvement in the detection efficiency of the detection system and failing to achieve the goal of shortening the incubation time. Therefore, the temperature difference configuration according to the present invention not only meets the requirement of suitable storage temperature to prevent denaturation of effective components, but also ensures the shortening of the system incubation reaction time and the sufficiency of the reaction.

[0054] This invention constructs a dual-temperature-controlled automated biological sample analysis system by integrating a reagent turntable, a sample turntable / tube transfer mechanism, a reagent dispensing unit, a sample dispensing unit, a reaction plate, and a controller. The reagent turntable can be a first reagent turntable and a second reagent turntable, respectively using thermoelectric cooling and refrigerant cooling for temperature control. The first reagent turntable is equipped with a central toothed disc and toothed structure to achieve uniform suspension of magnetic beads and reagents through self-rotation. The second reagent turntable is equipped with an identification window and an identifier to complete the identification of reagent tube group information. The controller has a built-in control mode decision unit and an interactive control unit, which can detect the system status and switch between dual target temperatures. In detection mode, the reagent turntable operates at 13–18℃, and in test mode, it operates at 2–8℃. Reagent transfer is only performed in the first target temperature mode. Without modifying the hardware structure, this system improves the initial temperature of the reaction system, shortens the incubation time, and enhances detection efficiency and result accuracy. Simultaneously, it ensures stable reagent preservation during the test period, solving problems such as slow incubation due to low-temperature reagents and easy dripping contamination when the dispensing head is heated. It can be used for fully automated high-precision detection and analysis of biological samples such as chemiluminescence immunoassay.

[0055] The above description, in conjunction with specific preferred embodiments, provides a further detailed explanation of the present invention. It should not be construed that the specific implementation of the present invention is limited to these descriptions. For those skilled in the art, various simple deductions or substitutions can be made without departing from the concept of the present invention, and all such modifications and substitutions should be considered within the scope of protection of the present invention.

Claims

1. An automated temperature control system for biological sample analysis, characterized in that, include: Reagent turntable, sample relay unit, reagent dispensing unit, sample dispensing unit, reaction tray, controller; The reagent turntable is used to hold reagents and can be either a first reagent turntable or a second reagent turntable. The sample relay unit is used for placing and transferring samples, and the sample relay unit includes a sample turntable or a sample tube transfer mechanism; The reaction plate is used to receive samples and reagents for reaction; the reagent dispensing unit is located near the reagent turntable and is used to transfer reagents from the reagent turntable to the reaction plate; the sample dispensing unit is located near the sample relay section and is used to transfer samples from the sample relay section to the reaction plate. The controller is electrically connected to the reagent turntable and is used to detect the current state of the system and control the reagent turntable to operate at a target temperature according to the current state of the system. The controller includes an interactive control unit, which is used to control the reagent dispensing unit to transfer reagents from the reagent turntable operating at a first target temperature to the reaction plate, and to control the reagent dispensing unit not to transfer reagents when the reagent turntable is operating at a second target temperature. The second target temperature is lower than the first target temperature.

2. The automated temperature control system for biological sample analysis according to claim 1, characterized in that, The reagent turntable is a first reagent turntable, which includes: a first reagent receiving cavity for accommodating reagent tube groups; a first driving mechanism disposed at the bottom of the first reagent receiving cavity for driving the first reagent receiving disk to rotate; the first reagent receiving disk is separately disposed at the upper part of the bottom of the first reagent receiving cavity; the first reagent receiving disk is provided with a plurality of locking areas for locking reagent tube groups; and a reagent loading port is provided on the side wall of the first reagent receiving cavity for transmitting reagent tube groups into the reagent receiving cavity via the reagent delivery rail. A first refrigeration unit is also attached to the bottom of the first reagent receiving cavity. The first refrigeration unit is used to output cold energy to the first reagent receiving cavity to maintain its internal temperature.

3. The automated temperature control system for biological sample analysis according to claim 2, characterized in that, A central toothed disk is also fixedly disposed inside the first reagent receiving cavity. The central toothed disk is separately disposed on the upper part of the first reagent receiving disk. The first reagent receiving disk is also provided with tooth-shaped structures evenly spaced around the circumference of the central toothed disk, which are used to mesh with and connect the bottom tooth-shaped structures of the magnetic bead storage well unit.

4. The automated temperature control system for biological sample analysis according to claim 2, characterized in that, The reagent tube assembly is preferably a spindle-shaped or boat-shaped structure, and the reagent tube assembly is provided with a number of reagent well units, which are preferably arranged in a straight line.

5. The automated temperature control system for biological sample analysis according to claim 1, characterized in that, The reagent turntable is a second reagent turntable, which includes: a second reagent receiving cavity for accommodating reagent tube groups; a second driving mechanism is disposed at the bottom of the second reagent receiving cavity for driving the rotation of the second reagent receiving turntable; the second reagent receiving turntable is provided with a plurality of reagent slots for securing reagent tube groups; an identification window is provided on the side wall of the second reagent receiving cavity; an identifier is fixedly disposed at a relative position outside the identification window for identifying reagent tube group information passing through the identification window. A second refrigeration unit is also attached to the bottom of the second reagent receiving chamber. The second refrigeration unit is used to output cooling energy to the second reagent receiving chamber to maintain its internal temperature. The second refrigeration unit includes a refrigeration section for supplying liquid cooling refrigerant, which removes waste heat.

6. The automated temperature control system for biological sample analysis according to claim 2, characterized in that, The first refrigeration unit is preferably a thermoelectric cooler. The cold end of the thermoelectric cooler is attached to the bottom of the first reagent receiving chamber and outputs cooling energy to the first reagent receiving chamber to maintain its internal temperature. The hot end of the thermoelectric cooler is connected to heat dissipation fins and carries away waste heat through convection air.

7. The automated temperature control system for biological sample analysis according to claim 1, characterized in that, The reaction plate is also equipped with a heating element for outputting heat to the reaction plate to adjust the incubation reaction temperature, which is set to 37°C.

8. The automated temperature control system for biological sample analysis according to claim 1, characterized in that, The sample relay unit includes a sample turntable. The reagent turntable and the sample turntable are arranged in a triangle on both sides of the reaction plate. The running trajectories of the reagent dispensing unit and the sample dispensing unit are tangent to different sides of the triangle formed by the reagent turntable, the sample turntable and the reaction plate, so as to avoid the trajectory crossing and causing reagent or sample contamination.

9. The automated temperature control system for biological sample analysis according to claim 1, characterized in that, The controller also includes a control mode decision unit, which is used to control the reagent turntable to operate at a first target temperature or a second target temperature.

10. A control method applied to an automated biological sample analysis temperature control system according to any one of claims 1-9, characterized in that, Includes the following steps: The controller detects the current system status and controls the reagent turntable to operate at the target temperature based on the current system status. When the system is currently in sample detection mode, the controller controls the first or second refrigeration unit to make the reagent turntable operate at a first target temperature, which is 13-18℃. When the system is currently in sample testing mode, the controller controls the first or second refrigeration unit to make the reagent turntable operate at a second target temperature, which is 2-8℃.

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