Serum neutralization experiment automation system and method

Abstract

The invention discloses a serum neutralization experiment automation system and method, and relates to the technical field of serum neutralization experiments. The system comprises a biological safety cabinet, an automatic operation module arranged in a closed operation space of the biological safety cabinet, and a control module in communication connection with the operation module, the automatic operation module comprises an XYZ mechanical arm unit, a pipetting unit mounted on the XYZ mechanical arm unit, a consumable bearing unit for placing experimental consumables and a reaction incubation unit for bearing and incubating a reaction container; the control module is configured to control the XYZ mechanical arm unit and the pipetting unit, and automatically complete the operations of taking and placing consumables from the consumable bearing unit, transferring liquid into the reaction container and transferring the reaction container between the consumable bearing unit and the reaction incubation unit. Through integrated full-automatic operation, the pathogen exposure risk of operators is remarkably reduced, manual errors are reduced, and the standardization degree, the result consistency and the data traceability of the experimental process are improved.

Description

An automated system and method for serum neutralization experiments Technical Field

[0001] This invention relates to the field of serum neutralization test technology, and in particular to an automated system and method for serum neutralization tests. Background Technology

[0002] Virus serum neutralization assays are a key technique for assessing the level of specific neutralizing antibodies in serum, and play an irreplaceable role in infectious disease diagnosis, vaccine efficacy evaluation, viral pathogenicity research, and biopharmaceutical quality control.

[0003] In existing technologies, the conventional operation mode of virus serum neutralization experiments is highly dependent on manual operation. Researchers must perform a series of complex steps within a biosafety cabinet, including sample dilution, virus-serum mixing, cell inoculation, incubation, and result interpretation. This traditional manual approach has gradually revealed several limitations over long-term use. First, due to the numerous steps and complete reliance on manual labor, experimental throughput is severely limited, making it difficult to meet the needs of large-scale sample screening or rapid testing in emergency outbreaks. Furthermore, researchers must handle samples that may contain live viruses directly within the biosafety cabinet for extended periods, posing a significant risk of pathogen exposure. Personal safety protection relies primarily on the passive protection of the biosafety cabinet and the operator's adherence to procedures, lacking more proactive engineered isolation measures. Moreover, manual liquid transfer and dilution operations inevitably introduce subjective errors, leading to poor repeatability and consistency of experimental results, affecting the reliability and comparability of data, and failing to meet the requirements of high-precision scientific research analysis and clinical diagnosis. Furthermore, the entire experimental process involves a large amount of manual recording, making it difficult to achieve full, real-time, and tamper-proof traceability of experimental data and operational procedures, which poses challenges in meeting increasingly stringent laboratory quality management and biosafety standards. Summary of the Invention

[0004] The technical problem to be solved by the embodiments of the present invention is: how to provide an integrated system solution that can achieve full automation of the virus serum neutralization experiment and high-precision operation requirements while ensuring high biosafety.

[0005] To address the aforementioned problems, in a first aspect, embodiments of the present invention propose an automated serum neutralization experiment system, comprising: a biosafety cabinet forming a closed operating space; an automated operation module disposed within the closed operating space; and a control module communicatively connected to the automated operation module; wherein the automated operation module includes an XYZ robotic arm unit, a pipetting unit mounted on the XYZ robotic arm unit, a consumable carrier unit for placing experimental consumables, and a reaction incubation unit for carrying and incubating reaction containers; the control module is configured to control the XYZ robotic arm unit and the pipetting unit to automatically perform operations such as picking up and placing consumables from the consumable carrier unit, transferring liquids into the reaction container, and transferring the reaction container between the consumable carrier unit and the reaction incubation unit.

[0006] Optionally, the automated operation module further includes a vision recognition unit, which is used to locate and / or identify the status of experimental consumables on the consumable carrying unit, and the control module is used to control the XYZ robotic arm unit to perform operations based on the recognition result of the vision recognition unit.

[0007] Optionally, the pipetting unit includes a precision pipetting mechanism and replaceable pipetting tips, wherein the precision pipetting mechanism is capable of aspirating and dispensing microliters of liquid according to a preset program.

[0008] Optionally, the consumable carrying unit includes a sample tube stage for carrying sample tubes, a well plate holder for carrying multi-well plates, a pipette tip box for accommodating pipette tips, and a liquid storage tank for holding liquid reagents.

[0009] Optionally, the reaction incubation unit includes an incubation chamber with temperature control function and an oscillation platform disposed in the incubation chamber. The oscillation platform is used to support the reaction vessel and oscillate during the incubation process.

[0010] Optionally, the automated operation module further includes a waste collection unit, which includes a collection box for collecting waste consumables and an in-situ sensor for detecting whether the collection box is in place or full.

[0011] Optionally, the biosafety cabinet is a Class II biosafety cabinet that meets the A2 standard, and the biosafety cabinet is equipped with an ultraviolet sterilization lamp.

[0012] Secondly, embodiments of the present invention propose a fully automated method for laboratory serum neutralization experiments using the system described in the first aspect, comprising the following steps: placing serum sample tubes, multi-well plates, pipette tips, and reagents containing virus solution and culture medium in preset positions on the consumables carrying unit; under the control of the control module, driving the XYZ robotic arm unit to cooperate with the pipetting unit to execute an automated operation sequence: removing the cover plate of the multi-well plate, using the pipetting unit to serially dilute the serum sample and transfer it into the multi-well plate, adding virus solution to designated wells of the multi-well plate, adding culture medium, and completing the sample addition process. The multi-well plate is transferred to the reaction incubation unit; in the reaction incubation unit, the multi-well plate containing the mixed reaction system is incubated at a constant temperature with shaking to complete the serum neutralization reaction; after incubation, the multi-well plate is removed from the reaction incubation unit; at the same time, the XYZ robotic arm unit is driven to transfer the used pipette tips and sample tube caps to the waste collection unit; throughout the operation, the control module automatically records process data including sample volume, incubation parameters and time, and uploads the process data to an external system after the operation is completed, generating a standardized experimental report based on the process data.

[0013] Optionally, before executing the automated operation sequence, the following steps are also included: acquiring images of each experimental consumable on the consumable carrying unit through a visual recognition unit, identifying and determining the precise position and state of each consumable; and the control module planning the motion path and operation coordinates of the XYZ robotic arm unit based on the recognition results.

[0014] Optionally, after the experimental report is generated, the following steps are also included: turning on the ultraviolet sterilization lamp in the biosafety cabinet to sterilize the enclosed operating space by irradiation for a predetermined period of time.

[0015] Compared with existing technologies, the technical effects achieved by the embodiments of the present invention include: the technical solution of the present invention effectively addresses the main challenges of traditional manual operation modes by combining the sealed protective space of the biosafety cabinet with the fully automated operation module integrated therein. This system utilizes a control module to uniformly coordinate the XYZ robotic arm unit and the pipetting unit, realizing fully automated operation from consumable handling and precise liquid transfer to reaction containers for incubation and transport. On the one hand, this liberates laboratory personnel from repetitive manual operations directly facing pathogens, significantly reducing the risk of pathogen exposure during operation. On the other hand, the mechanized operation sequence replaces manual steps, eliminating operational inconsistencies introduced by personnel fatigue and individual differences, thereby improving the standardization of experimental procedures and the reproducibility of results. Attached Figure Description

[0016] The accompanying drawings, which are incorporated in and form part of this specification, illustrate embodiments consistent with the invention and, together with the description, serve to explain the principles of the invention.

[0017] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, for those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0018] One or more embodiments are illustrated by way of example with reference numerals in the accompanying drawings. These illustrations do not constitute a limitation on the embodiments. Elements with the same reference numerals in the drawings are denoted as similar elements. Unless otherwise stated, the figures in the drawings are not to be limited by scale.

[0019] Figure 1 is a schematic diagram of the structure of an automated serum neutralization test system proposed in an embodiment of the present invention; Figure 2 is another schematic diagram of the structure of an automated serum neutralization test system proposed in an embodiment of the present invention; Figure 3 is a schematic diagram of the structure of an automated serum neutralization test system proposed in an embodiment of the present invention after the outer shell is removed; Figure 4 is an enlarged view of region A in Figure 3; Figure 5 is another schematic diagram of the structure of an automated serum neutralization test system proposed in an embodiment of the present invention after the outer shell is removed; Figure 6 is a schematic diagram of the structure of a waste collection unit of an automated serum neutralization test system proposed in an embodiment of the present invention; Figure 7 is a block diagram of the control principle of an automated serum neutralization test system proposed in an embodiment of the present invention.

[0020] The attached diagram shows the following components: 1. Biosafety cabinet; 2. Control module; 3. XYZ robotic arm unit; 4. Pipetting unit; 5. Consumables carrying unit; 6. Reaction incubation unit; 7. Vision recognition unit; 8. Precision pipetting mechanism; 9. Pipette tip; 10. Sample tube stage; 11. Well plate holder; 12. Tip box; 13. Liquid storage tank; 14. Waste collection unit; 15. Storage box; 16. In-situ sensor; 17. Electric gripper device. Detailed Implementation

[0021] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Similar component reference numerals in the drawings represent similar components. Obviously, the embodiments described below are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0022] It should be understood that, when used in this specification and the appended claims, the terms "comprising" and "including" indicate the presence of the described features, integrals, steps, operations, elements and / or components, but do not exclude the presence or addition of one or more other features, integrals, steps, operations, elements, components and / or collections thereof.

[0023] It should also be understood that the terminology used in this specification of embodiments of the invention is for the purpose of describing particular embodiments only and is not intended to limit the embodiments of the invention. As used in this specification of embodiments of the invention and the appended claims, the singular forms “a,” “an,” and “the” are intended to include the plural forms unless the context clearly indicates otherwise.

[0024] Referring to Figures 1-7, this embodiment of the invention proposes an automated system for serum neutralization experiments, comprising: a biosafety cabinet 1, forming a closed operating space; an automated operation module, disposed within the closed operating space; and a control module 2, communicatively connected to the automated operation module. The automated operation module includes an XYZ robotic arm unit 3, a pipetting unit 4 mounted on the XYZ robotic arm unit 3, a consumable carrier unit 5 for placing experimental consumables, and a reaction incubation unit 6 for carrying and incubating reaction containers. The control module 2 is configured to control the XYZ robotic arm unit 3 and the pipetting unit 4 to automatically perform operations such as retrieving and placing consumables from the consumable carrier unit 5, transferring liquids into the reaction container, and transferring the reaction container between the consumable carrier unit 5 and the reaction incubation unit 6.

[0025] In practice, the biosafety cabinet 1 constitutes a closed operating space, used to isolate the internal operating process from the external laboratory environment. All automated operating modules are installed inside this closed operating space.

[0026] Furthermore, the automated operation module includes an XYZ robotic arm unit 3, a pipetting unit 4, a consumables carrying unit 5, and a reaction incubation unit 6. The XYZ robotic arm unit 3, for example, is a multi-axis robotic arm mounted on a fixed base within the operating space, capable of movement in the X, Y, and Z degrees of freedom. The pipetting unit 4 is fixedly mounted at the end effector of the XYZ robotic arm unit 3 and moves along with it. The consumables carrying unit 5 is fixedly mounted on the worktable within the operating space and includes multiple dedicated positions or supports for positioning and placing different experimental consumables. The reaction incubation unit 6 is also fixedly mounted within the operating space and has the function of maintaining a specific temperature and motion state; the number of reaction incubation units 6 can be one, two, or three.

[0027] Furthermore, the control module 2 is located in a secure position outside or inside the biosafety cabinet 1, and is connected to the various electronic control components in the automated operation module via a wired or wireless communication interface. The control module 2 stores pre-written experimental procedure control programs. During operation, the control module 2 sends motion commands to the XYZ robotic arm unit 3, controlling it to move to designated positions in the consumables carrying unit 5. The control module 2 controls the gripping mechanism at the end of the XYZ robotic arm unit 3 to grasp or release consumables, such as sample tubes or pipette tips 9. Simultaneously, the control module 2 controls the pipetting unit 4 to perform precise liquid aspiration and dispensing actions. The control module 2 also coordinates the movement of the XYZ robotic arm unit 3 to transfer the reaction vessel, after sample loading, from the area of ​​the consumables carrying unit 5 and place it in the reaction incubation unit 6, and then transfers it back after incubation.

[0028] Furthermore, control module 2 allows users to customize and store experimental procedures, and is compatible with various sizes of multi-well plates, sample tubes, centrifuge tubes, and other commonly used laboratory consumables. Optionally, control module 2 has a built-in programmable logic controller (PLC) or industrial computer to run preset serum neutralization experimental procedures. These procedures include parameters such as step sequence, pipetting volume, incubation time, and temperature, which users can edit and call through a human-machine interface. In addition, the system can be equipped with a standard data interface for easy connection to a laboratory information management system, supporting automatic integration and full-process traceability of experimental data. Due to its fully automated operation, this system can significantly improve experimental efficiency, for example, reducing the time required to complete a single batch of 96-well plate experiments from several hours using traditional manual methods to less than several hours, and increasing the daily sample processing capacity to several hundred samples.

[0029] This embodiment combines the airtight protection function of the biosafety cabinet 1 with its integrated automated operation module to construct a complete automated experimental platform. The control module 2 coordinates the XYZ robotic arm unit 3 and the pipetting unit 4, replacing the traditional manual operations within the biosafety cabinet and achieving full automation from retrieving and placing consumables to transferring liquids to reaction containers. This integrated and automated design firstly liberates experimental personnel from directly interacting with pathogens, significantly reducing occupational exposure risks. Furthermore, mechanized operations replace manual steps, reducing errors introduced by operator fatigue or differences in skill level, thus improving the consistency and repeatability of the experimental process. Moreover, the entire system is physically self-contained, confining core steps such as sample processing and reaction incubation within a controlled, enclosed space, effectively reducing the possibility of aerosol leakage or cross-contamination and enhancing the overall biosafety level of the laboratory.

[0030] In some preferred embodiments, the end effector of the XYZ robotic arm unit 3 is equipped with an electric gripper device 17, which can be adapted to and grip various experimental consumables, including but not limited to multi-well plate covers, multi-well plate bodies, liquid storage tanks, centrifuge tubes, sample tubes, etc. The present invention is not specifically limited to these.

[0031] The electric gripper device 17 includes a gripping drive mechanism, a gripper assembly, and a gripping force sensor. The gripping drive mechanism is driven by a servo motor or stepper motor, which in turn drives the gripper assembly to open and close via a transmission mechanism. The gripper assembly can be designed with replaceable gripper heads according to the size and shape of different consumables, or it can adopt an adaptive gripper structure. Its gripping surface has anti-slip textures or a soft buffer layer to enhance gripping stability and avoid damage to the consumable surface. The gripping force sensor is integrated into the gripper assembly or drive mechanism to monitor the gripping force in real time and feed the signal back to the control module. The control module dynamically adjusts the output torque of the gripping drive mechanism according to a preset gripping force threshold and the type of consumable, achieving safe and stable gripping of consumables of different materials, shapes, and weights. Furthermore, the electric gripper device 17 can also be equipped with a rotating mechanism, allowing it to adjust the posture of the consumable during gripping, facilitating opening, tilting, or transfer operations.

[0032] In some preferred embodiments, the automated operation module further includes a visual recognition unit 7, which is used to locate and / or identify the status of experimental consumables on the consumable carrying unit 5, and the control module 2 is used to control the XYZ robotic arm unit 3 to perform operations based on the recognition result of the visual recognition unit 7.

[0033] In specific implementation, the visual recognition unit 7 includes one or more industrial cameras and a matching light source, fixedly installed on the top or side of an enclosed operating space, ensuring its field of view covers the main area of ​​the consumable carrying unit 5. The industrial cameras are connected to an image processing unit. The image processing unit can be integrated into the control module 2 or be a separate processor; this invention is not specifically limited. Before the experiment begins or after the consumables are placed, the control module 2 triggers the visual recognition unit 7 to operate. The industrial cameras capture images of the area of ​​the consumable carrying unit 5, and the image processing unit analyzes the images. The analysis process includes identifying the contour features of different consumables such as sample tubes, perforated plates, and suction head boxes 12 in the images, and calculating their precise center positions and angles relative to the XYZ coordinate system of the robotic arm unit 3.

[0034] Furthermore, image processing can also identify the status of consumables, such as determining whether the suction head box 12 is empty. The control module 2 receives the consumable position and status recognition results sent by the vision recognition unit 7. The control module 2 does not rely on preset fixed coordinates, but dynamically plans or corrects the specific motion path and end-effector coordinates of the XYZ robotic arm unit 3 to grasp or operate based on these real-time recognition results, thereby driving the XYZ robotic arm unit 3 to perform precise operations.

[0035] In this embodiment, a visual recognition unit 7 is introduced to provide the automated system with real-time environmental perception and feedback capabilities. The system automatically determines the precise pose of various consumables through image recognition, so that the operation of the XYZ robotic arm unit 3 no longer depends on the consumables being placed in extremely precise, fixed positions, reducing the stringent requirements for manual placement accuracy and improving the system's flexibility and fault tolerance. Furthermore, by recognizing the status of consumables, such as the presence or absence of a suction head or the status of the tube cap, the system can perform pre-checks before executing steps, avoiding operational errors or process interruptions caused by missing or abnormal consumables, thus enhancing the system's reliability and intelligence. Furthermore, dynamic path planning based on visual feedback enables the XYZ robotic arm unit 3 to adaptively complete grasping and manipulation, improving the robustness of the entire automated process and the final accuracy of the operation.

[0036] In some preferred embodiments, the pipetting unit 4 includes a precision pipetting mechanism 8 and a replaceable pipetting tip 9, wherein the precision pipetting mechanism 8 is capable of aspirating and dispensing microliters of liquid according to a preset program.

[0037] In practice, the pipetting unit 4 includes a precision pipetting mechanism 8 and replaceable pipette tips 9. The precision pipetting mechanism 8 is fixedly mounted at the end of the XYZ robotic arm unit 3 and contains a high-precision piston pump or syringe pump mechanism driven by a microstepping motor or piezoelectric ceramic driver. The pipetting unit 4 includes a liquid channel and has an interface at its end for connection to the pipette tips 9. The control module 2 is communicatively connected to the precision pipetting mechanism 8 and can send commands to the precision pipetting mechanism 8 to precisely control the displacement of its driving components, thereby achieving precise aspiration and dispensing of microliter or even nanoliter volumes of liquid. Specifically, through a high-precision driving mechanism and closed-loop control, the pipetting unit 4 can achieve the transfer of microliter-level liquids, with single-step pipetting accuracy reaching microliter levels and repeatability errors controlled at a low level to meet the requirements for precise liquid volume control in steps such as serum dilution series.

[0038] Thanks to the use of full-process automation and high-precision control, the system can significantly reduce human error and keep the coefficient of variation (CV) of experimental results at a low level (e.g., less than 8%), thus significantly improving the repeatability and reliability of the data.

[0039] Furthermore, the replaceable pipette tips 9 are disposable sterile consumables, typically arranged in rows in the tip holder 12 on the consumables carrying unit 5. When a pipetting operation is required, the control module 2 controls the XYZ robotic arm unit 3 to move the precision pipetting mechanism 8 above the tip holder 12, and through a vertical downward mechanical action, tightly connects the interface at the end of the pipetting mechanism to a pipette tip 9. After the liquid transfer operation is completed, the XYZ robotic arm unit 3 moves above the waste collection unit 14, and discards the used pipette tip 9 through a specific detachment mechanism or impact rod.

[0040] In this embodiment, a high-precision piston pump or syringe pump is used as the core of the pipetting mechanism. Its driving components are precisely controlled by digital signals, enabling highly repeatable pipetting of extremely small volumes of liquid. The volumetric error range is significantly lower than that of traditional manual pipettes or low-precision pumps, fundamentally ensuring the accuracy of key steps such as serum dilution and virus addition, which is a prerequisite for obtaining reliable neutralizing antibody titer data. Furthermore, replaceable disposable pipette tips 9 are used and automatically replaced after each sample addition step, completely eliminating potential cross-contamination between different samples or reagents via pipette tips and ensuring the independence of each experimental unit.

[0041] In some preferred embodiments, the consumable carrying unit 5 includes a sample tube stage 10 for carrying sample tubes, a well plate holder 11 for carrying multi-well plates, a pipette tip box 12 for accommodating pipette tips 9, and a liquid storage tank 13 for holding liquid reagents.

[0042] In specific implementation, the consumable support unit 5 includes a sample tube stage 10, a plate holder 11, a pipette tip box 12, and a liquid storage tank 13. The sample tube stage 10 is a support with multiple circular grooves or clamps, used to stably place serum sample cryopreservation tubes or centrifuge tubes of different sizes.

[0043] Furthermore, the perforated plate holder 11 is a tray or frame that matches the shape of a standard perforated plate, such as a 96-hole plate, for securing the perforated plate and preventing it from moving.

[0044] Furthermore, the pipette tip box 12 is used to hold rows of pipette tips 9. It is usually a standardized laboratory consumable and can be placed directly on the flat surface of the support unit or in the corresponding slot. There can be one or more pipette tip boxes 12.

[0045] Furthermore, the liquid storage tank 13 is used to hold liquid reagents, such as viral stock solution, cell culture medium or diluent. The liquid storage tank 13 can be a reagent tank with one or more compartments. The number of liquid storage tanks 13 can be one or more, and the specifications are different.

[0046] The aforementioned components are arranged in a modular fashion on the workbench inside the biosafety cabinet 1, forming a fixed preparation area for experimental consumables. Their relative positions are pre-mapped and entered into the control module 2, or calibrated by the visual recognition unit 7, so that the XYZ robotic arm unit 3 and the pipetting unit 4 can be precisely positioned during operation.

[0047] In this embodiment, the sample tube stage 10 ensures that the slender sample tubes remain upright and stable during operation, facilitating the robotic arm's opening and sample aspiration operations. Furthermore, the dedicated well plate holder 11 prevents the lightweight multi-well plate from sliding or shifting during sample addition or transfer, ensuring accurate sample placement. Moreover, the standardized pipette tip box 12 and reservoir 13 design allows the system to be compatible with commercially available consumables, reducing consumable costs and operational complexity for users.

[0048] In some preferred embodiments, the reaction incubation unit 6 includes an incubation chamber with temperature control function and an oscillation platform disposed within the incubation chamber, the oscillation platform being used to support the reaction container and oscillate during the incubation process.

[0049] In practice, the reaction incubation unit 6 includes an incubation chamber and an oscillation platform. The incubation chamber is a closed or semi-closed space with insulated walls. Heating elements (such as electric heating films) and temperature sensors are installed inside, forming a closed-loop temperature control system that can maintain the air temperature inside the chamber at a constant set value, such as 37 degrees Celsius.

[0050] Furthermore, the oscillation platform is located inside the incubation chamber and is driven by a drive motor, eccentric wheel, or linear motor, enabling it to perform circular or linear reciprocating motion on a horizontal plane. The oscillation platform is equipped with a holder or elastic clamp that matches the size of the perforated plate for fixing the plate in place.

[0051] Furthermore, control module 2 is connected to the temperature control system of the incubation chamber and the drive motor of the oscillation platform. When incubation is required, control module 2 activates the temperature control system to preheat and maintain the temperature, while simultaneously controlling the oscillation platform to oscillate continuously or intermittently at a set frequency and amplitude. The multi-well plate undergoes a mixed reaction of serum and virus under constant temperature and oscillation conditions.

[0052] In this embodiment, the constant temperature control function provides a standard and stable temperature environment for the neutralization reaction, which is a key condition for ensuring the normal progress of the virus-antibody binding reaction. Furthermore, the built-in oscillation function keeps the liquid in the multi-well plate slightly mixed throughout the reaction process, promoting sufficient and uniform contact between serum and virus particles, avoiding local concentration differences or incomplete reactions caused by standing, and helping to improve reaction efficiency and uniformity.

[0053] In some preferred embodiments, the automated operation module further includes a waste collection unit 14, which includes a collection box 15 for collecting waste consumables and an in-situ sensor 16 for detecting whether the collection box 15 is in place or full.

[0054] In practice, the waste collection unit 14 includes a collection box 15 and an in-situ sensor 16. The collection box 15 is a container that can be placed on the work surface inside the biosafety cabinet 1 to collect solid waste such as used pipette tips 9, discarded sample tube caps, and empty sample tubes.

[0055] Furthermore, the presence sensor 16 can be a mechanical microswitch, an infrared photoelectric sensor, or a capacitive proximity switch, installed at or next to the predetermined position of the storage box 15. The presence sensor 16 is electrically connected to the control module 2. When the storage box 15 is correctly placed in the predetermined position, the presence sensor 16 generates a signal indicating that the storage box 15 is in place and available. Furthermore, the control module 2 checks this signal first when driving the XYZ robotic arm unit 3 to perform the waste disposal action. During the disposal process, the XYZ robotic arm unit 3 moves the gripped waste consumables above the opening of the storage box 15 and releases them.

[0056] Furthermore, some in-situ sensors 16 can also determine whether the storage box 15 is full by monitoring the height of the waste accumulation or the state of obstruction, and send a full box signal to the control module 2 to prompt the user to replace it.

[0057] In this embodiment, the XYZ robotic arm unit 3 automatically collects used consumables into designated containers, avoiding the need for operators to frequently open the window of the biosafety cabinet 1 to manually clean up waste. This significantly reduces the chances of personnel coming into contact with potential contaminants and lowers biosafety risks. Furthermore, the presence sensor 16 provides a status feedback function, ensuring that the system only performs the disposal operation when the storage box 15 is correctly positioned. This prevents waste from scattering and contaminating the cabinet due to a missing storage box 15, improving system reliability. Additionally, the full-box indicator function helps to ensure timely emptying and prevent waste overflow.

[0058] In some preferred embodiments, the biosafety cabinet 1 is a Class II biosafety cabinet 1 that conforms to the A2 standard, and the biosafety cabinet 1 is equipped with an ultraviolet sterilization lamp.

[0059] In its implementation, Biosafety Cabinet 1 adopts a Class II Biosafety Cabinet 1 structure conforming to Type A2 standards. Internally, it maintains a directional airflow pattern: air from the external environment flows into the operating space through a high-efficiency particulate air filter, then exits through an exhaust air filter within the operating space, protecting samples, personnel, and the environment. The high-efficiency particulate air filter meets the relevant standards for particulate matter filtration. The construction and performance of Biosafety Cabinet 1 comply with general requirements for laboratory biosafety (e.g., GB19489-2008) and relevant standards for Class II Biosafety Cabinets 1 (e.g., YY 0569-2011). Both its inlet and outlet air are equipped with high-efficiency particulate air filters, with a filtration efficiency of not less than 99.995%, effectively ensuring a safe operating environment.

[0060] Furthermore, an ultraviolet (UV) sterilization lamp is installed on the top or rear side of the inner wall of the operating space of the biosafety cabinet 1. The power supply of the UV sterilization lamp is connected to the control module 2 or an independent timer controller. After the experiment is completed, the operator closes the front window of the biosafety cabinet and leaves, the UV sterilization lamp can be activated through the interface of the control module 2 or an external controller to irradiate all exposed surfaces inside the empty enclosed operating space for a predetermined time. Furthermore, the radiation intensity and irradiation time of the UV sterilization lamp are set to achieve effective disinfection of the surfaces inside the enclosed operating space; for example, the radiation intensity of the UV lamp at a distance of 1 meter can reach 107 μW / cm². 2 above.

[0061] In this embodiment, an A2-type Class II biosafety cabinet is used as the system foundation, ensuring that the entire automated operation process is carried out within a protective device that complies with international and domestic biosafety standards. Its directional airflow and high-efficiency filtration system provide reliable physical isolation and removal capabilities for any potentially infectious aerosols, a fundamental safety prerequisite for handling viral samples. Furthermore, an ultraviolet (UV) sterilization lamp is added, providing a highly efficient, chemical-residue-free terminal disinfection method. After each daily batch of experiments is completed, automatic or manual triggering of UV irradiation effectively inactivates microorganisms, including viruses and bacteria, that may remain on the cabinet's work surface, equipment surface, and internal air, further eliminating the potential risks of cross-contamination and personnel exposure.

[0062] This invention proposes a fully automated operation method for laboratory serum neutralization experiments using the above system, including the following steps: S1, placing the serum sample tube, multi-well plate, pipette tip, and reagents containing virus solution and culture medium in a preset position of the consumables carrying unit.

[0063] S2, under the control of the control module, drives the XYZ robotic arm unit to cooperate with the pipetting unit to execute an automated operation sequence: remove the cover plate of the multi-well plate, use the pipetting unit to serially dilute the serum sample and transfer it into the multi-well plate, add virus solution to the designated wells of the multi-well plate, add culture medium, and transfer the multi-well plate after sample addition to the reaction incubation unit.

[0064] S3, in the reaction incubation unit, a multi-well plate containing a mixed reaction system is incubated under constant temperature and vibration to complete the serum neutralization reaction.

[0065] S4. After incubation is complete, remove the multiwell plate from the reaction incubation unit; at the same time, drive the XYZ robotic arm unit to transfer the used pipette tips and sample tube caps to the waste collection unit.

[0066] S5. During the entire operation, the control module automatically records process data including sample volume, incubation parameters and time, and uploads the process data to an external system after the operation is completed, generating a standardized experimental report based on the process data.

[0067] In practice, the operator first places the sample tube containing the serum to be tested, the empty or pre-filled multi-well plate containing diluent, the pipette tip, and the reagent tube or reservoir containing virus solution and cell culture medium into the preset corresponding positions in the consumables carrying unit inside the biosafety cabinet, and then closes the front window of the biosafety cabinet.

[0068] After the system is started, the following automated operation sequence is executed under the control of the control module. The XYZ robotic arm unit first moves to above the perforated plate. The control module drives the electric gripper device to adjust the gripping force and position according to the current object being manipulated, such as gripping the edge or protruding structure of the perforated plate cover. The control module drives the electric gripper device to close to clamp the cover, and then controls the XYZ robotic arm unit to lift vertically, thereby separating the cover from the perforated plate body. Subsequently, the XYZ robotic arm unit moves the removed cover horizontally to a separate cover storage rack located on one side of the work area, and places the cover in the slot of the rack, completing the removal and temporary storage of the cover.

[0069] Next, liquid handling operations are performed. Driven by the XYZ robotic arm, the pipetting unit first moves to above the tip holder and picks up a clean pipette tip. Then, the XYZ robotic arm positions itself above the sample tube, and the pipetting unit descends, inserting the tip below the liquid surface of the sample tube to aspirate a predetermined volume of serum. The XYZ robotic arm then moves the pipetting unit to above the first well of the multi-well plate (e.g., well A1), where the pipetting unit injects serum into this well, which may be pre-filled with diluent to initiate the dilution process. For serial dilutions, the pipetting unit can replace the tip or use the same tip (according to the program settings) to aspirate the mixture from the first well and transfer it to the next well for continuous dilution, thus creating a series of serum concentration gradients in different wells of the multi-well plate.

[0070] Further, after serum dilution and aliquoting, the pipetting unit is replaced with a new pipette tip. The XYZ robotic arm unit moves the pipetting unit above the reservoir containing the virus solution and aspirates a predetermined volume of virus solution. Subsequently, the XYZ robotic arm unit precisely positions itself above each well in the multi-well plate that already contains diluted serum, and the pipetting unit sequentially adds an equal volume of virus solution to each well, mixing the serum and virus within the well.

[0071] Next, the pipetting unit is replaced with a new pipette tip. The XYZ robotic arm unit moves the pipetting unit above the reservoir containing cell culture medium and aspirates the medium. The pipetting unit adds a predetermined volume of culture medium to each designated well of the multi-well plate to provide a suitable environment for cell growth.

[0072] Further, after all liquid addition steps are completed, the XYZ robotic arm unit moves to the cover plate storage rack and uses an electric gripper to retrieve the perforated plate cover plate. The XYZ robotic arm unit moves the cover plate above the perforated plate and aligns it, then lowers and replaces the cover plate on the perforated plate to reduce evaporation and contamination. Next, the end effector of the XYZ robotic arm unit switches to a gripper suitable for holding the perforated plate, grasps the entire perforated plate with the cover plate already on, removes it from the perforated plate holder in the consumables carrier unit, and smoothly transfers and places it on the oscillation platform holder within the reaction incubation unit.

[0073] Furthermore, within the reaction incubation unit, the control system activates temperature control and oscillation functions. The temperature inside the incubation chamber is maintained at a constant value, for example, within the range of 37.0 ± 0.5 degrees Celsius. Simultaneously, the oscillation platform continuously oscillates at a set frequency and amplitude, keeping the liquid within the multi-well plate homogenized and promoting the serum neutralization reaction. Incubation continues for a preset time period.

[0074] Furthermore, after the incubation reaches the predetermined time, the reaction incubation unit stops oscillating. The XYZ robotic arm unit moves back into the reaction incubation unit, uses a perforated plate clamp to grasp the entire perforated plate, removes it from the oscillation platform, and transfers it back to a designated output position on the consumable carrier unit, or a dedicated finished product storage area, for the operator to retrieve later for result observation or analysis.

[0075] Furthermore, waste disposal procedures are performed simultaneously with or after the experimental operation. The XYZ robotic arm unit, using its end-effector's electric gripper or a dedicated waste tip unloading lever, removes used pipette tips from the pipetting unit and places them into the waste collection box. Similarly, other solid waste, such as any empty sample tube caps, is also collected in this box.

[0076] Furthermore, throughout the execution of the entire operation sequence, the control module automatically and in real-time records key data related to the experimental process. This data includes, but is not limited to: the actual volume aspirated and dispensed by the pipetting unit in each step, the coordinates of the multi-well plate corresponding to each sample addition operation, the volume and well position of the added virus solution and culture medium, the actual temperature profile of the reaction incubation unit, and the start and end times of incubation. This process data is stored in association with sample identifiers.

[0077] Furthermore, after all the preset operation sequences have been executed, the control module will automatically upload the stored process data to the connected laboratory information management system or the designated data server through its integrated data communication interface (such as Ethernet or serial port).

[0078] Furthermore, the control module or its linked host computer software integrates sample information, experimental process parameters, raw operation data, and timestamps based on a pre-set report template, and automatically generates a structured, standard-format experimental report document. The report may include tables and summary data.

[0079] In this embodiment, multiple independent steps that were originally scattered and relied on human experience for judgment and execution are integrated into a coherent and controlled procedural process. The automated operation sequence ensures that each sample undergoes a completely consistent dilution, addition, and mixing process, fundamentally eliminating variables such as omissions, sequence errors, or inaccurate timing caused by manual operation. This greatly improves the standardization of the experimental process and the comparability of results between different batches. Furthermore, the automatic recording and uploading of experimental data enables digital traceability of the entire experimental process. Parameters at any step can be verified, enhancing data reliability and compliance, and meeting stringent quality management system requirements. Furthermore, the automatic report generation function rapidly transforms experimental results into structured documents, significantly shortening the cycle from the end of the experiment to obtaining analysis results, improving overall work efficiency, and providing strong support for time-sensitive applications such as rapid diagnosis and vaccine evaluation.

[0080] In some preferred embodiments, before executing the automated operation sequence, the following steps are also included: acquiring images of each experimental consumable on the consumable carrying unit through a visual recognition unit, identifying and determining the precise position and state of each consumable; and the control module planning the motion path and operation coordinates of the XYZ robotic arm unit based on the recognition results.

[0081] In practice, after the operator places all consumables and starts the system, the control module first triggers the vision recognition unit. The industrial camera of the vision recognition unit captures an image of the area where the consumables are carried, and the image processing unit processes and analyzes the image. The analysis process includes identifying the visual features of different types of consumables in the image, such as identifying objects like sample tubes, multi-well plates, pipette tip boxes, and liquid storage tanks through edge detection and pattern matching. For each identified object, the precise two-dimensional or three-dimensional coordinates of its center point in the robotic arm coordinate system and its rotation angle are calculated.

[0082] Furthermore, status analysis can be performed, such as determining whether any pipette tips are missing from the tip box or whether the sample tube caps are open. The control module receives these recognition results from the vision recognition unit, including the precise position coordinates and status information of each consumable. Subsequently, the control module uses this real-time, accurate coordinate information to plan the motion path and target position of the end effector for each specific action performed by the XYZ robotic arm unit, such as grasping, moving, and adding samples, replacing the reliance on preset fixed coordinates.

[0083] In this embodiment, the system no longer requires operators to place consumables precisely in preset positions with millimeter-level accuracy. Instead, it allows for arbitrary placement within a certain range, with the vision system automatically identifying and locating them. This reduces the precision requirements of manual operation, simplifies the preparation process, and improves the user-friendliness and startup efficiency of the method. Furthermore, motion planning based on real-time visual feedback enables the robotic arm to adaptively respond to minor changes in the actual position of the consumables, such as those caused by manufacturing tolerances or placement deviations. This ensures precise alignment with the target in every operation, significantly improving the robustness of the entire method at the execution level and the final operational accuracy. Furthermore, the status recognition function acts as a pre-inspection step, detecting missing consumables or abnormal statuses before critical operations are performed, avoiding invalid operations or failures, and enhancing the intelligence and reliability of the method.

[0084] In some preferred embodiments, after the experimental report is generated, the following steps are also included: turning on the ultraviolet sterilization lamp in the biosafety cabinet to sterilize the enclosed operating space by irradiation for a predetermined period.

[0085] In practice, once the entire experimental procedure is completed and the operator has confirmed through the control interface or the system has automatically determined that an experimental cycle has been completed, the control module can send a start command to the ultraviolet sterilization lamp circuit inside the biosafety cabinet.

[0086] Alternatively, the operator can manually initiate this step through a sterilization procedure interface independent of the experimental process. The ultraviolet (UV) sterilization lamps are activated, irradiating all exposed areas within the enclosed operating space with UV light. Irradiation continues for a predetermined time period, such as thirty minutes. At the end of this period, the control module or timer automatically shuts off the UV sterilization lamps.

[0087] Furthermore, in some embodiments, this disinfection step can be combined with the interlocking device of the biosafety cabinet to ensure that the ultraviolet lamp can only be activated when the front window of the biosafety cabinet is completely closed and there is no human intervention, so as to ensure safety.

[0088] In this embodiment of the invention, by controlling the timed irradiation of the ultraviolet lamp through a program, it is possible to ensure that the interior space of the biosafety cabinet undergoes an effective disinfection process after each experiment, unaffected by human factors, thereby reliably inactivating any remaining pathogenic microorganisms. This effectively eliminates the risk of cross-contamination between batches, providing a clean and safe starting environment for the next experimental batch or experiments with different samples.

[0089] In the above embodiments, the descriptions of each embodiment have different focuses. For parts that are not described in detail in a certain embodiment, please refer to the relevant descriptions in other embodiments.

[0090] In the description of this invention, it should be understood that the terms "center," "longitudinal," "lateral," "length," "width," "thickness," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," "clockwise," and "counterclockwise," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only 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 specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this invention.

[0091] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of this invention, "a plurality of" means two or more, unless otherwise explicitly specified.

[0092] In this invention, unless otherwise explicitly specified and limited, the terms "installation," "connection," "linking," and "fixing," etc., should be interpreted broadly. For example, they can refer to a connection, a detachable connection, or an integral part; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal communication of two components or the interaction between two components. Those skilled in the art can understand the specific meaning of the above terms in this invention according to the specific circumstances.

[0093] In this invention, unless otherwise explicitly specified and limited, "above" or "below" the second feature can include direct contact between the first and second features, or contact between the first and second features through another feature between them. Furthermore, "above," "over," and "on top" of the second feature includes the first feature directly above or diagonally above the second feature, or simply indicates that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature includes the first feature directly below or diagonally below the second feature, or simply indicates that the first feature is at a lower horizontal level than the second feature.

[0094] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the invention. The illustrative expressions of the above terms in this specification should not be construed as necessarily referring to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. In addition, those skilled in the art can combine and integrate the different embodiments or examples described in this specification.

[0095] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Since these modifications and variations fall within the scope of the claims and their equivalents, this invention also intends to include these modifications and variations.

[0096] The above description describes specific embodiments of the present invention, but the scope of protection of the present invention is not limited thereto. Any person skilled in the art can easily conceive of various equivalent modifications or substitutions within the technical scope disclosed in the present invention, and these modifications or substitutions should all be covered within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. An automated system for serum neutralization experiments, characterized in that, include: Biosafety cabinets create a closed operating space; An automated operation module is located within the enclosed operating space; a control module is communicatively connected to the automated operation module; wherein, the automated operation module includes an XYZ robotic arm unit, a pipetting unit mounted on the XYZ robotic arm unit, a consumable carrier unit for placing experimental consumables, and a reaction incubation unit for carrying and incubating the reaction vessel; the control module is configured to control the XYZ robotic arm unit and the pipetting unit to automatically complete operations such as picking up and placing consumables from the consumable carrier unit, transferring liquids into the reaction vessel, and transferring the reaction vessel between the consumable carrier unit and the reaction incubation unit.

2. The automated serum neutralization test system according to claim 1, characterized in that, The automated operation module further includes a vision recognition unit, which is used to locate and / or identify the status of experimental consumables on the consumable carrying unit. The control module is used to control the XYZ robotic arm unit to perform operations based on the recognition results of the vision recognition unit.

3. The automated serum neutralization test system according to claim 1, characterized in that, The pipetting unit includes a precision pipetting mechanism and replaceable pipetting tips. The precision pipetting mechanism is capable of aspirating and dispensing microliters of liquid according to a preset program.

4. The automated serum neutralization test system according to claim 1, characterized in that, The consumables carrying unit includes a sample tube stage for carrying sample tubes, a well plate holder for carrying multi-well plates, a pipette tip box for accommodating pipette tips, and a liquid storage tank for holding liquid reagents.

5. The automated serum neutralization test system according to claim 1, characterized in that, The reaction incubation unit includes an incubation chamber with temperature control function and an oscillation platform disposed in the incubation chamber. The oscillation platform is used to support the reaction container and oscillate during the incubation process.

6. The automated serum neutralization test system according to claim 1, characterized in that, The automated operation module also includes a waste collection unit, which includes a collection box for collecting waste consumables and an in-situ sensor for detecting whether the collection box is in place or full.

7. The automated serum neutralization test system according to claim 1, characterized in that, The biosafety cabinet is a Class II biosafety cabinet that meets the A2 standard, and it is equipped with an ultraviolet sterilization lamp.

8. A fully automated method for laboratory serum neutralization experiments using the system described in any one of claims 1 to 7, characterized in that, The process includes the following steps: placing serum sample tubes, multi-well plates, pipette tips, and reagents containing virus solution and culture medium in preset positions on the consumables carrying unit; under the control of the control module, driving the XYZ robotic arm unit to cooperate with the pipetting unit to execute an automated operation sequence: removing the cover of the multi-well plate, using the pipetting unit to serially dilute the serum sample and transfer it into the multi-well plate, adding virus solution and culture medium to designated wells of the multi-well plate, and transferring the multi-well plate after sample addition to the reaction incubation unit; in the reaction incubation unit, incubating the multi-well plate containing the mixed reaction system at a constant temperature with shaking to complete the serum neutralization reaction; after incubation, removing the multi-well plate from the reaction incubation unit; simultaneously, driving the XYZ robotic arm unit to transfer used pipette tips and sample tube caps to the waste collection unit; Throughout the operation, the control module automatically records process data, including sample volume, incubation parameters, and time. After the operation is completed, the process data is uploaded to an external system, and a standardized experimental report is generated based on the process data.

9. The fully automated operation method for laboratory serum neutralization experiments according to claim 8, characterized in that, Before executing the automated operation sequence, the following steps are also included: acquiring images of each experimental consumable on the consumable carrying unit through the visual recognition unit, identifying and determining the precise position and status of each consumable; the control module plans the motion path and operation coordinates of the XYZ robotic arm unit based on the recognition results.

10. The fully automated operation method for laboratory serum neutralization experiments according to claim 8, characterized in that, After the experimental report is generated, the following steps are also included: turning on the ultraviolet sterilization lamp in the biosafety cabinet to sterilize the enclosed operating space by irradiation for a predetermined period of time.

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