Full-automatic glycosylated hemoglobin separation and purification device

Abstract

The invention belongs to the technical field of biological detection, and particularly discloses a full-automatic glycosylated hemoglobin separation and purification device which is used for solving the problems existing in glycosylated hemoglobin separation and purification. The device specifically comprises a separation and purification box, a box door is mounted at one end of the separation and purification box, a first mounting plate is fixed to the other side of the separation and purification box, on one hand, the position and height of a sampling needle are adjusted through a first motor and an electric push rod, and the sampling needle can conveniently suck a sample and put the sample into a hematolysis box; the hemolysis box, the filter cartridge and the chromatographic column are cleaned through a mixing rod, a second transmission pump and a first transmission pump, so that the glycosylated hemoglobin is convenient to separate and purify; on the other hand, the sample tube can be fixed through the spring and the check block, displacement of the sample tube is avoided, the sample tube is pushed to ascend through the supporting plate, the sample tube is conveniently taken out, and therefore the sample tube is conveniently assembled and disassembled.

Description

Technical Field

[0001] This invention relates to the field of biological detection technology, and in particular to a fully automated glycated hemoglobin separation and purification device. Background Technology

[0002] Glycated hemoglobin (HbA1c), a stable product formed from the non-enzymatic glycation of hemoglobin and glucose within red blood cells, is irreversibly generated and persists throughout the red blood cell's lifespan. This indicator objectively reflects the average blood glucose concentration over the past 2-3 months, thus possessing significant clinical value in diabetes screening, diagnosis, and long-term glycemic control assessment. Due to the complex composition of blood samples, HbA1c detection requires the initial extraction of the target component from whole blood through separation and purification steps. The purification effect directly impacts the accuracy and reliability of subsequent analytical results. Commonly used purification methods include ion exchange chromatography, affinity chromatography, and high-performance liquid chromatography (HPLC). While these methods possess specificity, their effectiveness is highly dependent on the standardization of the operational process and the stability of the equipment.

[0003] In current separation and purification technologies, most operations still rely on manual labor, including sample pipetting, column processing, centrifugation, and buffer replacement. This primarily manual operation mode is not only prone to operational errors due to differences in operator skill, affecting result reproducibility, but also results in a lengthy and inefficient overall process. The bottleneck effect of manual operation is particularly pronounced in scenarios involving large-volume sample processing. Its high labor intensity and tedious steps increase the risk of human error, making it difficult to meet the growing demands of modern clinical testing for high throughput, standardization, and traceability. Furthermore, manual operations are more sensitive to environmental cleanliness, temperature, and humidity conditions, further increasing the difficulty of quality control.

[0004] Furthermore, existing separation and purification equipment has significant shortcomings in terms of maintenance and cleaning. Instruments require thorough cleaning before and after each use to prevent cross-contamination, but most current equipment designs require manual disassembly for effective cleaning. This process increases the mechanical workload of operators and may lead to component wear or assembly errors due to frequent disassembly and reassembly. Simultaneously, complex piping structures and cleaning dead spots at interfaces can easily harbor contaminant residues, posing a potential risk to subsequent test results. In addition, existing equipment often lacks automatic cleaning and disinfection modules, making it difficult to achieve closed-loop cleaning validation, further impacting the overall operational efficiency and compliance level of the laboratory. Therefore, there is an urgent need to improve the automation, integration, and intelligence of the glycated hemoglobin separation and purification process through technological optimization and equipment improvement, thereby significantly improving experimental efficiency and reducing the workload of operators while ensuring the accuracy and reproducibility of test results. Summary of the Invention

[0005] The present invention aims to provide a fully automated glycated hemoglobin separation and purification device. By integrating functional modules for precise sampling and pipetting, programmed online cleaning, and rapid positioning and clamping of sample tubes, the device achieves automated operation, efficient cleaning, and convenient loading and unloading of the separation and purification process, thereby improving detection efficiency, result consistency, and operational convenience.

[0006] The objective of this invention can be achieved through the following technical solution: A fully automated glycated hemoglobin separation and purification device, comprising a separation and purification chamber, a door installed at one end of the separation and purification chamber, a first mounting plate fixed to the outside of the other side of the separation and purification chamber, a control box fixed to the lower end of the first mounting plate, a second mounting plate and a third mounting plate fixed to the two sides inside the separation and purification chamber respectively, a hemolysis tank for hemolysis reaction fixed to the upper end of the second mounting plate, a first transfer pump fixed to the lower end of the second mounting plate, a filter cartridge and a chromatographic column fixed to the bottom inside the separation and purification chamber respectively, a collection cartridge for collecting purified components installed on one side of the bottom inside the separation and purification chamber, a sealing cylinder fixed to the upper end of the separation and purification chamber, a mixing tank fixed to the upper end of the first mounting plate, and multiple sets of sample tubes for containing blood samples to be tested detachably installed inside the third mounting plate. The separation and purification device of the present invention integrates core functional modules such as a blood lysis chamber, a filter cartridge, a chromatographic column, and a collection cartridge, creating a closed, fully automated operating environment. It can complete the entire process of hemolysis, filtration, chromatographic separation, and product collection of glycated hemoglobin on an integrated platform, effectively avoiding human operation errors and sample cross-contamination, and significantly improving the consistency and reliability of detection results.

[0007] Preferably, a first motor is fixed to the other side of the sealed cylinder. The output shaft of the first motor is connected to a screw arranged in a horizontal direction. A moving plate is threaded onto the screw. An electric push rod is fixed to the upper end of the moving plate. A lifting plate is fixed to the lower end of the push rod of the electric push rod. Multiple sampling needles corresponding to the positions of the sample tubes are arranged at the lower end of the lifting plate. A second motor is fixed to the other side of the mixing box. The output shaft of the second motor extends into the mixing box and is connected to a mixing rod. A second transfer pump is fixed to the lower end of the mixing box. A pipe is connected to the outlet of the second transfer pump. This invention achieves precise positioning and automatic liquid transfer of the sampling needles in three-dimensional space through the coordinated control of the first motor, screw, electric push rod, and sampling needles, completing the automated sample transfer and delivery from the sample tube to the blood coagulation box. At the same time, the automatic preparation and delivery of the cleaning solution is achieved in conjunction with the mixing box, the second transfer pump, and other structures, reducing manual intervention and improving the efficiency and standardization of sample pretreatment.

[0008] Preferably, the inlet of the first transfer pump is connected to the bottom of the blood coagulation chamber via a pipe, and its outlet is connected to the inlet of the filter cartridge via a pipe; the outlet of the filter cartridge is connected to the inlet of the chromatographic column via a pipe; the outlet of the chromatographic column can be selectively connected to the collection cartridge or a waste liquid collection device. This solution, by rationally planning the pipe connections between the first transfer pump, the filter cartridge, and the chromatographic column, forms a continuous and directional separation and purification flow path, ensuring that the sample flows sequentially through each processing unit in a closed system. This not only reduces sample loss and contamination risk but also optimizes the fluid path, improving separation efficiency and product recovery rate.

[0009] Preferably, the outlet end of the pipeline extends into the separation and purification chamber and is located directly above the blood lysis chamber. The control box contains a controller, which is electrically connected to the first motor, the second motor, the electric actuator, the first transfer pump, and the second transfer pump, respectively, to control the various components to work collaboratively according to a predetermined program. Here, the pipeline outlet is precisely positioned directly above the blood lysis chamber, and the controller allows for centralized programming control of each actuator, enabling the sequential and collaborative operation of steps such as sampling, liquid addition, mixing, and cleaning. This enhances the accuracy of system operation and the repeatability of the process, providing a stable and reliable automated solution for batch sample processing.

[0010] Preferably, multiple sets of vertically arranged sliding rods are fixed inside the separation and purification chamber near the third mounting plate. Side plates are slidably sleeved on the sidewalls of the sliding rods. Multiple sets of springs are arranged on the sidewalls facing the inner sidewall of the separation and purification chamber. Stops corresponding to the number and position of the sample tubes are fixed on the sidewalls facing the sample tubes. A telescopic cylinder is fixed at the lower end of the third mounting plate corresponding to the position of each sample tube, and a support plate is installed at the lower end of the telescopic cylinder. This design, through the combined design of sliding rods, side plates, springs, stops, telescopic cylinders, and support plates, constructs an elastic clamping and lifting mechanism for the sample tubes. While ensuring the sample tubes remain in a fixed position during operation and preventing displacement or tipping, it also enables rapid loading and unloading of the sample tubes, significantly improving loading and unloading efficiency and operational convenience.

[0011] Preferably, when the side plate is in its natural state, the stop is located directly above the corresponding sample tube opening, forming an axial limit; one end of the spring is connected to the inner wall of the separation and purification chamber, and the other end is connected to the side plate, providing the side plate with an elastic restoring force towards the sample tube. Here, the elastic restoring force of the spring is used to automatically reset the stop and form a stable axial limit on the sample tube, achieving reliable fixation without additional locking operations. The structure is simple and the operation is reliable, simplifying the operation steps and avoiding sample tube damage or inaccurate positioning caused by uneven human tightening force.

[0012] Preferably, the support plate is located directly below the sample tube, and the telescopic cylinder is a pneumatic or electric telescopic cylinder, electrically connected to the controller in the control box to drive the support plate to rise and fall; the installation position of the sample tube on the third mounting plate corresponds precisely to the position of the sampling needle below the lifting plate in vertical projection. This solution achieves programmed lifting control of the support plate by electrically connecting the telescopic cylinder to the controller, allowing the sample tube to be smoothly lifted when removed, further optimizing the human-computer interaction experience; at the same time, the precise vertical projection correspondence design between the sample tube and the sampling needle ensures that the sampling needle can be accurately inserted into the sample tube, improving the success rate and accuracy of automatic sampling.

[0013] Preferably, an ultrasonic generator is integrated inside or at the bottom of the hemolysis chamber. This ultrasonic generator is electrically connected to a controller within the control box and is used to perform ultrasonic treatment during or after mixing the sample with the hemolytic agent to promote the hemolysis reaction. By integrating an ultrasonic generator into the hemolysis chamber, the ultrasonic oscillation can accelerate the disruption of red blood cells and the release of hemoglobin, shortening the hemolysis reaction time and improving hemolysis efficiency and uniformity. This provides a more stable and sufficient sample pretreatment basis for subsequent separation and purification steps.

[0014] Preferably, the top of the mixing tank is provided with a cleaning fluid inlet and a pure water inlet, for connecting to the cleaning fluid source and the pure water source, respectively; the blades of the mixing rod are multi-layered inclined paddle-type structures to optimize the mixing efficiency of the cleaning fluid and water. This invention, by setting separate cleaning fluid and pure water inlets in the mixing tank and employing a multi-layered inclined paddle-type mixing rod structure, can achieve precise, rapid preparation and uniform mixing of the cleaning fluid concentration, ensuring stable and consistent cleaning results and providing reliable assurance for the online cleaning of key system components.

[0015] Preferably, electrically controlled valves are installed on the connecting pipe between the filter cartridge and the chromatographic column, as well as on the outlet pipe of the chromatographic column; the collection cartridge is placed on a weighable sensor, which is electrically connected to the controller to monitor the volume or mass of the collected purified product. This invention, by installing electrically controlled valves at key flow path nodes and combining them with a weighing sensor to monitor the collected product, achieves precise control of the fluid path in the separation and purification process and real-time monitoring of the product collection amount. This not only improves the flexibility of process control but also provides reliable data support for quantitative analysis of the results.

[0016] Compared with existing plans, the present invention has the following advantages: 1. This invention achieves precise sampling and pipetting operations through an automated mechanical structure, significantly improving the standardization of the separation and purification process. Specifically, a forward-starting electric actuator drives the lifting plate and sampling needle vertically downward, allowing the sampling needle to accurately insert into the sample tube and aspirate a quantitative sample. Subsequently, the reverse-starting electric actuator resets the sampling needle. Then, the forward-starting first motor, through screw transmission, drives the moving plate and sampling needle horizontally to directly above the hemolysis chamber, completing the delivery and mixing of the sample and hemolysing agent. This design, through the coordinated control of the first motor and the electric actuator, achieves precise positioning and movement of the sampling needle in three-dimensional space, not only avoiding the volume errors and contamination risks associated with manual sampling but also significantly improving the efficiency and consistency of sample pretreatment.

[0017] 2. This invention integrates a fully automated cleaning system, enabling programmed cleaning of key components, effectively preventing cross-contamination and reducing manual intervention. A second motor drives a mixing rod to uniformly mix the cleaning solution in the mixing tank, then a second transfer pump sprays the cleaning solution into the blood coagulation tank. Subsequently, the first transfer pump is activated, causing the cleaning solution to flow sequentially through the filter cartridge and chromatographic column, completing the online flushing of the entire separation and purification flow path. This system achieves comprehensive cleaning of the internal flow path without disassembling the equipment, eliminating potential component damage or assembly errors caused by manual cleaning, and ensuring the cleanliness of the equipment between different batches of tests, thereby guaranteeing the stability and reliability of glycated hemoglobin detection results.

[0018] 3. This invention features an easy-to-operate sample tube positioning and clamping mechanism, improving loading and unloading efficiency and ensuring sample stability during processing. When placing the sample tube, the side plate moves the stop block laterally and compresses the spring, creating an unobstructed space above the third mounting plate, allowing the sample tube to be placed vertically until it contacts the support plate. After releasing the side plate, the spring returns to its original position, pushing the stop block back into place and fixing the sample tube from above. When removing the sample tube, the side plate is reversed to release the obstruction, allowing the support plate to lift the sample tube upwards for easy sequential placement and removal. This positioning and clamping mechanism, through the synergistic action of the spring and the stop block, achieves rapid positioning and stable clamping of the sample tube, preventing displacement or tipping during operation, while simplifying loading and unloading steps and facilitating continuous, batch sample processing. Attached Figure Description

[0019] The invention will be further described below with reference to the accompanying drawings: Figure 1 This is a perspective view of the fully automated glycated hemoglobin separation and purification device of the present invention; Figure 2 This is a schematic diagram of the internal structure of the separation and purification chamber in this invention; Figure 3 This is a schematic diagram of the internal structure of the mixing box in this invention; Figure 4This is a schematic diagram of the connection structure between the third mounting plate and the support plate in this invention; Figure 5 This is a block diagram of the circuit structure of the controller in this invention.

[0020] Legend: 1. Separation and purification chamber; 2. Chamber door; 3. First mounting plate; 4. Control box; 5. Second mounting plate; 6. Blood lysis chamber; 7. First transfer pump; 8. Filter cartridge; 9. Chromatographic column; 10. Collection cartridge; 11. Sealing cartridge; 12. First motor; 13. Screw; 14. Moving plate; 15. Electric push rod; 16. Lifting plate; 17. Sampling needle; 18. Mixing chamber; 19. Second motor; 20. Mixing rod; 21. Second transfer pump; 22. Pipeline; 23. Third mounting plate; 24. Sample tube; 25. Sliding rod; 26. Side plate; 27. Spring; 28. Stop; 29. ​​Telescopic cylinder; 30. Support plate. Detailed Implementation

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

[0022] like Figures 1-5As shown, the fully automated glycated hemoglobin separation and purification device of the present invention consists of a separation and purification chamber 1 and multiple functional modules integrated therein. The separation and purification chamber 1 is made of medical-grade stainless steel, and one end of it is fitted with a hinged, sealable observation door 2 for easy equipment maintenance and sample loading by operators. A first mounting plate 3 is fixed to the outside of the other side of the chamber 1. Below the first mounting plate 3 is a control box 4 with an integrated control system and human-machine interface, used to realize automated control and status monitoring of the entire process. Inside the separation and purification chamber 1, a second mounting plate 5 and a third mounting plate 23 are fixed to both sides by fasteners. The second mounting plate 5 adopts a multi-layer structure design, with a blood lysis box 6 for standardized hemolysis reaction at the upper end and a high-precision first transfer pump 7 fixed at the lower end. The third mounting plate 23 is equipped with a modular sample rack, on which multiple sets of standard-sized sample tubes 24 for holding blood samples to be tested are detachably installed, supporting batch continuous processing. The bottom of the separation and purification chamber 1 is secured with a shock-resistant mounting base, housing two core separation units: a filter cartridge 8 and a chromatographic column 9. The filter cartridge 8 contains a multi-layer composite filter membrane, and the chromatographic column 9 is filled with specific adsorbent material. A labeled collection tube 10 is also located on one side of the chamber for the classified collection of target components at different purification stages. A sealed cylinder 11 is fixed to the top of the chamber via a guide rail mechanism to house and protect the precision sampling and moving mechanism. Above the first mounting plate 3, a mixing tank 18 with liquid level monitoring is fixed for the precise preparation of washing solutions of different concentrations.

[0023] The automated sampling and transfer function of the separation and purification device of this invention is achieved through a precision mechanical system. A servo motor 12 is mounted on the outside of the sealed cylinder 11 via a motor mount. The output shaft of the first motor 12 is connected to a high-precision ball screw 13 via a coupling. A movable plate 14, which engages with the screw 13 via a nut pair, can move smoothly on a linear guide rail. An adjustable-stroke electric push rod 15 is fixed on the movable plate 14. A lifting plate 16 at the lower end of the electric push rod 15 is equipped with multiple medical-grade sampling needles 17, precisely corresponding to the positions of the sample tubes 24 below, through a quick-change interface, supporting the aspiration of sample volumes of different specifications. Through a three-dimensional positioning system where the first motor 12 controls horizontal movement and the electric push rod 15 controls vertical lifting, the sampling needles 17 can automatically aspirate a quantitative sample from the sample tube 24 and precisely transfer it to the placement position above the blood dissolution box 6 via a preset path. In addition, the explosion-proof second motor 19 on the outside of the mixing box 18 drives the multi-layer inclined paddle mixing rod 20 inside the box to rotate through the sealed bushing, so as to achieve efficient and uniform mixing of the cleaning solution; the lower end of the mixing box 18 is connected to the second transfer pump 21 with pulsation suppression through the pipeline, which delivers the prepared cleaning solution to the top of the blood dissolution box 6 in the form of atomization or liquid column through the corrosion-resistant pipe 22.

[0024] The separation and purification device of this invention constructs a complete closed-loop fluid processing path. The inlet of the first transfer pump 7 is connected to the outlet at the bottom of the blood dissolution tank 6 via a medical silicone tube, and the outlet is connected to the inlet of the filter cartridge 8 and the waste liquid collection device via a three-way valve. The outlet of the filter cartridge 8 is connected to the inlet of the chromatographic column 9 via a pipeline. The outlet of the chromatographic column 9 can be selectively connected to the collection cartridge 10 or the waste liquid pipeline via a multi-way switching valve to achieve product fractionation and waste liquid separation. The first motor 12, the second motor 19, the electric actuator 15, the first transfer pump 7, the second transfer pump 21, and the control valves of each pipeline in this invention are all connected to the programmable controller in the control box 4 via cables. The controller coordinates the timing actions of each component according to a preset program to achieve fully automated operation from sample aspiration, hemolysis, filtration separation to chromatographic purification.

[0025] The controller integrated in control box 4 adopts a programmable logic controller (PLC) system based on an industrial standard architecture. Its core hardware uses the widely used Siemens S7-1200 series PLC module, which features multiple digital input / output channels, analog acquisition ports, and high-speed pulse output, meeting the control requirements of various motors, pumps, valves, and sensors. The controller connects to a touchscreen human-machine interface via a standard RS-485 communication bus, enabling interactive functions for parameter setting and status display. Simultaneously, the system is also equipped with a communication module compliant with the industrial Ethernet protocol, supporting data exchange with a laboratory information management system and meeting the standardized design requirements of modern automated equipment.

[0026] In terms of electrical connections, the controller establishes reliable connections with each actuator via pre-fabricated cables. Specifically, the drivers of the first motor 12, the second motor 19, and the electric actuator 15 are connected to the controller's digital output port via shielded control cables to transmit start / stop and direction control signals; the first transfer pump 7, the second transfer pump 21, and various solenoid valves are connected to the controller's output via relay modules to achieve on / off control. All sensor signals are connected to the controller's analog input channel via a signal conditioning module. All connectors use aviation plugs that meet IP67 protection standards to ensure the stability and safety of electrical connections in a laboratory environment.

[0027] The controller's core functions mainly include process timing control and status monitoring. In terms of process control, the controller's embedded program executes the following steps sequentially according to the preset glycated hemoglobin separation and purification process: sampling needle positioning, sample aspiration and transfer, hemolysis, filtration separation, chromatographic purification, and tubing cleaning. The execution time, motion parameters, and liquid processing volume for each step can be set and adjusted via the touchscreen interface. Regarding status monitoring, the controller collects data from various sensors in real time, monitoring sample processing progress, liquid flow rate and pressure, and equipment operating status. When an abnormality is detected, the system will automatically execute preset safety procedures and issue an alarm.

[0028] It is important to note that the control scheme employed in this device is based on mature industrial automation technology. The control logic is implemented using ladder logic programming language conforming to the IEC 61131-3 standard. This programming method has been used in the automation field for decades and is technically mature and reliable. The motion control section employs the classic "position-velocity-time" three-stage control algorithm, which is widely used in precision medical devices. The communication protocol uses standard Modbus RTU and TCP / IP protocols to ensure system compatibility and scalability. The entire control system used by the controller does not contain any unconventional or unproven technical solutions and fully conforms to the general understanding and expectations of those skilled in the art regarding automated equipment.

[0029] To ensure stable placement and convenient retrieval of the sample tubes 24, this device features a specialized clamping and lifting mechanism. On the inner wall of the housing near the third mounting plate 23, multiple vertically arranged linear slide rods 25 are fixed via mounting bases. Engineering plastic side plates 26 are slidably fitted onto the slide rods 25. The side of the side plate 26 facing away from the sample is connected to multiple sets of adjustable preload compression springs 27 via guide posts. The other end of the springs 27 is fixed to the inner wall of the housing. Elastic stops 28, corresponding to the number and position of the sample tubes 24, are embedded in the side of the side plate 26 facing the sample. Under the preload of the springs 27, the stops 28 press against the upper edge of the sample tube opening in a natural state, forming a reliable axial limit. A pneumatic or electric telescopic cylinder 29 is installed at the corresponding mounting position below each sample tube 24. The arc-shaped support plate 30 at its top matches the bottom contour of the sample tube 24. The telescopic cylinder 29 is connected to the control box 4 via a solenoid valve or driver, allowing the sample tube 24 to be smoothly lifted to a set height according to a program when the sample is retrieved. The clamping and lifting mechanism enables semi-automatic loading and unloading of sample tubes, significantly improving the efficiency and safety of batch sample processing.

[0030] To further optimize the processing effect and process control, this device also integrates several auxiliary functional units. The bottom of the hemolysis chamber 6 integrates an adjustable frequency ultrasonic generator, with its transducer array evenly distributed at the bottom. It can apply ultrasonic oscillations of a specific frequency during the hemolysis stage to accelerate red blood cell disruption and improve hemoglobin release efficiency. The top of the mixing chamber 18 is equipped with a cleaning solution inlet and a pure water inlet controlled by flow meters, which can be connected to an external supply system. Its internal multi-layer inclined paddle mixer 20 is made of 316L stainless steel, and achieves efficient and low-foaming mixing of the cleaning solution by optimizing the blade angle and interlayer spacing. At key nodes in the connecting pipeline between the filter cartridge 8 and the chromatographic column 9, as well as in the outlet pipeline of the chromatographic column 9, electrically controlled pinch valves or butterfly valves are installed for precise control of fluid path and flow rate. The collection cartridge 10 is placed on a high-precision weighing sensor, and the sensor signal is transmitted to the control system in real time, continuously monitoring the quality changes of the collected product and providing data support for quantitative analysis.

[0031] The fully automated glycated hemoglobin separation and purification device of this invention works by automatically completing the entire process from raw blood sample to purified product in a closed environment through an integrated mechanical structure, fluid path, and intelligent control system. Its core is to integrate the traditionally manual sampling, hemolysis, filtration, chromatographic separation, and washing steps into a coherent automated procedure to improve processing efficiency, result consistency, and operational reliability.

[0032] The specific working process begins with the automatic sampling and transport of samples. After the operator loads the sample rack containing multiple sample tubes 24 into the device and closes the door 2, the control system is activated. The first motor 12 drives the screw 13 to rotate, moving the moving plate 14 and the sampling needle 17 assembly fixed thereon horizontally to directly above the first sample tube 24. Subsequently, the electric push rod 15 drives the lifting plate 16 to descend, allowing the sampling needle 17 to be precisely inserted into the bottom of the sample tube 24, completing the quantitative sample aspiration. After the sampling needle 17 is reset, the first motor 12 again drives the moving plate 14 to move horizontally, positioning the sampling needle 17 directly above the hemolysis box 6, and injecting the sample into the reaction chamber pre-filled with hemolytic agent. This process is precisely coordinated by the controller, achieving unmanned and precise sample transfer.

[0033] After sample delivery, the device enters the sample processing and purification stage. The ultrasonic generator in the hemolysis chamber 6 is activated, accelerating red blood cell disruption through cavitation and promoting hemoglobin release. After hemolysis, the first transfer pump 7 is activated, delivering the mixture at a constant flow rate to the filter cartridge 8 to remove large particulate impurities such as cell debris. The filtrate then enters the chromatographic column 9, where the column packing material specifically adsorbs glycated hemoglobin, achieving separation of the target component from non-glycated hemoglobin and other impurities. By adjusting the pH and ionic strength of the buffer solution, the target component is selectively eluted and delivered by the first transfer pump 7 to the collection cartridge 10. A weighing sensor below the collection cartridge 10 monitors the product mass in real time, providing data for quantitative analysis.

[0034] After the entire process is completed or during batch processing intervals, this device executes a fully automated cleaning procedure to prepare for the next round of testing. The mixing tank 18 automatically draws in cleaning solution and pure water according to a preset ratio. The second motor 19 drives the mixing rod 20 to prepare the solution to the working concentration. The second transfer pump 21 sprays the cleaning solution through the pipeline 22 onto components such as the blood dissolution tank 6 and the sampling needle 17 for initial rinsing. Subsequently, the first transfer pump 7 drives the cleaning solution to flow sequentially through the filter cartridge 8 and the chromatographic column 9, dissolving and removing residual proteins and salts. All cleaning waste liquid is directed to a dedicated waste liquid collection device. Simultaneously, the sample tube loading and unloading mechanism operates synchronously under the coordination of the controller: the telescopic cylinder 29 lifts the processed sample tube 24, which can be easily removed by the operator by pulling the side plate 26, and a new batch of samples to be tested can be loaded. The entire process is carried out sequentially under the unified scheduling of the control system, with seamless integration of each step, achieving full automation, closed-loop management, and standardization of the glycated hemoglobin separation and purification process.

[0035] In the fully automated glycated hemoglobin separation and purification device of the present invention, the controller has a pre-stored optimized process program specifically designed for glycated hemoglobin separation and purification. This program is compiled based on industry standard operating procedures and a large amount of experimental verification data, transforming the complex biochemical separation process into a series of precise and controllable automated instruction sequences. It is the core of achieving standardized and high-throughput processing throughout the entire process, as detailed below: First, the program constructs a phased, configurable process flow framework. Logically, the entire program is divided into four main sequential modules: sample pretreatment, separation and purification, online cleaning, and system preparation. Each module contains several sub-steps with independently configurable parameters. For example, in the sample pretreatment module, operators can preset the sampling volume, hemolysin addition amount, and ultrasonic hemolysis time and power through the human-machine interface. The program allows the creation and storage of multiple process formulations for different testing standards or sample types, achieving processing flexibility.

[0036] Second, the program achieves precise timing control of key physical and chemical parameters. In the separation and purification module, the program precisely schedules the following core parameters: Fluid control: The first transfer pump 7 is controlled to deliver the hemolyzed sample to the filter cartridge 8 at a preset constant flow rate. During the chromatographic separation stage, the multi-channel solenoid valve is controlled to sequentially and proportionally switch the introduction of buffer solutions with different pH values ​​and ionic strengths to achieve specific adsorption and elution of the target components.

[0037] Motion control: The program coordinates the first motor 12 and the electric push rod 15 to ensure that the movement trajectory, speed, insertion depth and dwell time of the sampling needle 17 are executed according to the optimal path, so as to ensure sampling accuracy and avoid foam generation.

[0038] Energy control: The ultrasonic generator inside the blood dissolution chamber 6 is activated at specific steps by a program. Its working frequency, duty cycle and duration are all set by the program to achieve a highly efficient and gentle hemolysis effect and prevent protein denaturation.

[0039] Third, the program integrates closed-loop monitoring and feedback adjustment logic to ensure process stability and reliability.

[0040] Pressure monitoring: The flow path pressure is monitored in real time by pressure sensors installed at the inlet of filter cartridge 8 and column 9. The program has a built-in pressure safety threshold; when the pressure rises abnormally, the program will automatically pause and start the flushing subroutine or issue an alarm.

[0041] Liquid circuit monitoring: The program monitors the remaining amount of key reagents in real time through level sensors on mixing tank 18 and reagent storage bottles, and issues early warnings when the amount is insufficient to prevent process interruption.

[0042] Product collection judgment: Based on the weighing sensor data below the collection cylinder 10, the program can monitor the elution peak in real time. When the rate of change of eluent mass is detected to meet the preset target component collection conditions, the valve automatically switches to guide the effluent to the collection cylinder 10; otherwise, it guides it to waste liquid, thus realizing intelligent segmented collection of the product.

[0043] Fourth, the program incorporates comprehensive cleaning and system maintenance routines. The online cleaning module includes cleaning solutions for different levels of contamination. The program can automatically activate the second transfer pump 21 to flush the sampling needle 17, blood lysis tank 6, filter cartridge 8, and chromatographic column 9 flow path according to preset cleaning solution concentration, volume, flow rate, and number of cycles. The parameters, time, and final emptying of cleaning agent for all cleaning steps are automatically managed by the program to ensure no residue remains, preparing for the next test.

[0044] The optimized process is not a simple sequential control, but a comprehensive automated solution that integrates parameterized formula management, multi-axis motion coordination, timing logic control, sensor feedback adjustment, and intelligent diagnosis and maintenance. It fully encodes all the key technical decision points from sample to purified product, enabling the device to stably and repeatedly perform glycated hemoglobin separation and purification operations that meet the quality requirements of clinical testing.

[0045] In summary, this invention provides a highly integrated, fully automated glycated hemoglobin separation and purification device and process. This solution integrates the complex separation process traditionally reliant on manual labor into a single platform through a precise mechanical transmission system and modular fluid path design. It achieves closed-loop automation of the entire process, from automatic sample collection, standardized hemolysis, high-efficiency filtration and specific chromatographic separation, to online system cleaning and convenient sample rack loading and unloading. Its core lies in an optimized process program built into the controller. This program not only precisely coordinates the timing of each actuator but also achieves real-time monitoring and intelligent adjustment of key physical and chemical parameters through sensor feedback. This significantly improves throughput and operational convenience while ensuring the consistency and reliability of processing results. This device solves the prominent problems of large manual operation errors, cumbersome processes, and inconvenient cleaning in existing technologies, providing clinical laboratories with a stable, efficient, and standardized solution for glycated hemoglobin separation and purification.

[0046] The above description is merely an example and illustration of the structure of the present invention. Those skilled in the art can make various modifications or additions to the specific embodiments described, or use similar methods to replace them, as long as they do not deviate from the structure of the invention or exceed the scope defined in the claims, all of which should fall within the protection scope of the present invention.

Claims

1. A fully automated glycated hemoglobin separation and purification device, comprising a separation and purification chamber (1), characterized in that, The separation and purification box (1) is equipped with a door (2) at one end. A first mounting plate (3) is fixed to the outside of the other side of the separation and purification box (1). A control box (4) is fixed to the lower end of the first mounting plate (3). A second mounting plate (5) and a third mounting plate (23) are fixed to the two sides inside the separation and purification box (1). A blood lysis box (6) for hemolysis reaction is fixed to the upper end of the second mounting plate (5). A first transfer pump (7) is fixed to the lower end of the second mounting plate (5). A filter cartridge (8) and a chromatographic column (9) are fixed to the bottom inside the separation and purification box (1). A collection cartridge (10) for collecting purified components is installed on one side of the bottom inside the separation and purification box (1). A closed cartridge (11) is fixed to the upper end of the separation and purification box (1). A mixing box (18) is fixed to the upper end of the first mounting plate (3). Multiple sets of sample tubes (24) for holding blood samples to be tested are detachably installed inside the third mounting plate (23).

2. The fully automated glycated hemoglobin separation and purification device according to claim 1, characterized in that, A first motor (12) is fixed on the other side of the closed cylinder (11). The output shaft of the first motor (12) is connected to a screw (13) arranged in a horizontal direction. A moving plate (14) is threaded onto the screw (13). An electric push rod (15) is fixed at the upper end of the moving plate (14). A lifting plate (16) is fixed at the lower end of the push rod of the electric push rod (15). A plurality of sampling needles (17) corresponding to the position of the sample tube (24) are provided at the lower end of the lifting plate (16). A second motor (19) is fixed on the other side of the mixing box (18). The output shaft of the second motor (19) extends into the mixing box (18) and is connected to a mixing rod (20). A second transfer pump (21) is fixed at the lower end of the mixing box (18). A pipe (22) is connected to the outlet of the second transfer pump (21).

3. The fully automated glycated hemoglobin separation and purification device according to claim 1, characterized in that, The inlet of the first transfer pump (7) is connected to the bottom of the blood dissolution tank (6) through a pipe, and its outlet is connected to the inlet of the filter cartridge (8) through a pipe; the outlet of the filter cartridge (8) is connected to the inlet of the chromatographic column (9) through a pipe; the outlet of the chromatographic column (9) may be selectively connected to the collection cartridge (10) or the waste liquid collection device.

4. The fully automated glycated hemoglobin separation and purification device according to claim 2, characterized in that, The outlet end of the pipe (22) extends into the separation and purification box (1) and is located directly above the blood dissolution box (6); the control box (4) is equipped with a controller, which is electrically connected to the first motor (12), the second motor (19), the electric push rod (15), the first transfer pump (7) and the second transfer pump (21) respectively, and is used to control each component to work together according to a predetermined program.

5. The fully automated glycated hemoglobin separation and purification device according to claim 1, characterized in that, Inside the separation and purification chamber (1), near the third mounting plate (23), there are multiple sets of vertically arranged sliding rods (25). The side walls of the sliding rods (25) are slidably fitted with side plates (26). The side plates (26) facing the inner side wall of the separation and purification chamber (1) are provided with multiple sets of springs (27). The side plates (26) facing the sample tubes (24) are fixed with blocks (28) corresponding to the number and position of the sample tubes (24). The lower end of the third mounting plate (23) is fixed with telescopic cylinders (29) corresponding to the position of each sample tube (24). The lower end of the telescopic cylinders (29) is equipped with a support plate (30).

6. The fully automated glycated hemoglobin separation and purification device according to claim 5, characterized in that, When the side plate (26) is in its natural state, the stop (28) is located directly above the opening of the corresponding sample tube (24) to form an axial limit; one end of the spring (27) is connected to the inner wall of the separation and purification box (1), and the other end is connected to the side plate (26) to provide the side plate (26) with an elastic restoring force toward the sample tube (24).

7. The fully automated glycated hemoglobin separation and purification device according to claim 5, characterized in that, The support plate (30) is located directly below the sample tube (24), and the telescopic cylinder (29) is a pneumatic telescopic cylinder or an electric telescopic cylinder, which is electrically connected to the controller in the control box (4) to drive the support plate (30) to rise and fall; the installation position of the sample tube (24) on the third mounting plate (23) corresponds precisely to the position of the sampling needle (17) below the lifting plate (16) in the vertical projection.

8. The fully automated glycated hemoglobin separation and purification device according to claim 2, characterized in that, An ultrasonic generator is integrated inside or at the bottom of the blood dissolution box (6). The ultrasonic generator is electrically connected to the controller in the control box (4) and is used to perform ultrasonic treatment when or after the sample is mixed with the hemolytic agent to promote the hemolytic reaction.

9. The fully automated glycated hemoglobin separation and purification device according to claim 1, characterized in that, The top of the mixing tank (18) is provided with a cleaning fluid inlet and a pure water inlet, which are used to connect the cleaning fluid source and the pure water source, respectively; the blades of the mixing rod (20) are multi-layer inclined paddle-type structures to optimize the mixing efficiency of the cleaning fluid and water.

10. The fully automated glycated hemoglobin separation and purification device according to claim 3, characterized in that: Electrically controlled valves are installed on the connecting pipe between the filter cartridge (8) and the chromatographic column (9), as well as on the outlet pipe of the chromatographic column (9); the collection cartridge (10) is placed on a weighable sensor, which is electrically connected to the controller to monitor the volume or mass of the collected purified product.

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