A protein liquid treatment device and a protein liquid treatment method

Abstract

In the field of biomedical research and clinical diagnosis, there are many factors in the traditional processing device that amplify the protein aggregation and precipitation phenomenon, which seriously interferes with the accuracy and effect of separation and purification. The application provides a protein liquid processing device and a protein liquid processing method, which adopts a non-contact liquid level detection unit and optimizes the pipeline connection structure to avoid direct contact of the sample with mechanical parts and reduce fluid shear effect, thereby effectively inhibiting the protein aggregation and precipitation phenomenon.

Description

Technical Field

[0001] This application relates to biomedical sample processing technology, specifically to a protein liquid processing device and a protein liquid processing method. Background Technology

[0002] In the fields of biomedical research and clinical diagnosis, liquid biological samples such as blood, serum, and cell culture media widely contain a variety of functional proteins. The precise separation and efficient purification of these proteins are crucial for early disease screening, drug target validation, and the exploration of fundamental mechanisms of life activities, directly impacting the reliability of research results and the accuracy of medical diagnosis. However, during routine sample transfer, mixing, and filtration, protein molecules are susceptible to fluid shear forces, interfacial tension, and environmental fluctuations, leading to non-specific aggregation and irreversible precipitation. Simultaneously, biochemical reactions may continue, causing conformational changes or loss of biological activity in proteins. Traditional pump-valve systems commonly used in processing devices are prone to particle shedding during repeated deformation of the membrane material, and their complex internal flow channels cause sample retention and increased turbulence. These factors collectively amplify protein aggregation and precipitation, severely interfering with the precision and effectiveness of separation and purification. These technical deficiencies not only reduce the reproducibility of experimental data but also potentially lead to misdiagnosis in clinical practice, necessitating the development of novel processing solutions to mitigate these problems. Summary of the Invention

[0003] The purpose of this application is to provide a protein liquid processing device and a protein liquid processing method, which can effectively reduce protein aggregation and precipitation, and improve the accuracy and reliability of sample processing.

[0004] This application provides a protein liquid processing device, the technical solution of which is as follows: It includes a first pipeline, a second pipeline, a first sampling unit, a first liquid level detection unit, a second liquid level detection unit, a drive unit, and a membrane filtration unit. The drive unit includes a first port and a second port. The first nano-sampling unit includes a third port and a fourth port. The membrane filtration unit includes a fifth port and a sixth port. The second port of the drive unit is connected to the third port of the first nano-sample unit. The fourth port of the first sampling unit is connected to one end of the first pipeline. The other end of the first pipeline is connected to the fifth port of the membrane filtration unit. The sixth port of the membrane filtration unit is connected to one end of the second pipeline. The other end of the second pipe is connected to the first port of the drive unit. The first liquid level detection unit is installed on the outer wall of the first pipeline. The second liquid level detection unit is installed on the outer wall of the second pipeline. Both the first liquid level detection unit and the second liquid level detection unit are non-contact detection units.

[0005] Furthermore, this application also proposes that, Both the first liquid level detection unit and the second liquid level detection unit are acoustic field liquid level detection units. in, The response time of the acoustic field liquid level detection unit during air detection is less than 10ms. And / or, the response time of the acoustic field liquid level detection unit during liquid detection is less than 1 second.

[0006] Furthermore, this application also proposes that the ultrasonic intensity Ispta of the acoustic field liquid level detection unit is <100mW / cm. 2 , And / or, the response time of the acoustic field liquid level detection unit during liquid detection is greater than or equal to 10 times the response time of the acoustic field liquid level detection unit during air detection.

[0007] Furthermore, this application also proposes that both the first and second conduits are made of non-transparent materials. Both the first and second pipelines are made of bio-inert materials.

[0008] Furthermore, this application also proposes that, The protein solution processing device also includes a second sample preparation unit. The second sampling unit includes a seventh port and an eighth port. The other end of the second pipeline is connected to the seventh port of the second nano-sample unit. The eighth port of the second sampling unit is connected to the first port of the driving unit.

[0009] Furthermore, this application also proposes that, The distance from the detection point of the first liquid level detection unit to the end of the first pipeline connected to the first sampling unit is the length of the pipeline. The distance from the detection point to one end of the first pipeline connecting to the membrane filtration unit is greater than or equal to three times the length of the pipeline. And / or, The distance from the detection point of the second liquid level detection unit to the end of the second pipeline connecting to the second sampling unit is the length of the pipeline. The distance from the detection point to one end of the membrane filtration unit connected to the second pipeline is greater than or equal to three times the pipeline length.

[0010] Furthermore, this application also proposes that, The drive unit is a gas-driven device. And / or, the protein solution does not flow through the first port and the second port.

[0011] Furthermore, this application also proposes that the first sampling unit and / or the second sampling unit are provided with a sealing device. And / or, the protein liquid processing device also includes an atmospheric pressure port, which is equipped with an air filter.

[0012] Furthermore, this application also proposes that the drive unit includes a one-way pump, a first three-way valve, a second three-way valve, a third three-way valve, and a three-way interface. The output end of the unidirectional pump is connected to the common terminal of the first three-way valve. The normally open terminal of the first three-way valve is connected to the first terminal of the three-way connector. The second and third ends of the three-way connector are respectively connected to the normally open ends of the second and third three-way valves. The common terminals of the second three-way valve and the third three-way valve are the first port and the second port of the drive unit, respectively.

[0013] Furthermore, this application also proposes a protein liquid processing method for a protein liquid processing device, including a bidirectional co-drive step, in which the three-way interface is simultaneously connected to the common end of the second three-way valve and the third three-way valve, and / or the three-way interface is only connected to one of the common ends of the second three-way valve and the third three-way valve.

[0014] As can be seen from the above, the protein liquid processing device and method provided in this application include a first pipeline, a second pipeline, a first sample collection unit, a first liquid level detection unit, a second liquid level detection unit, a driving unit, and a membrane filtration unit. The driving unit includes a first port and a second port. The second port of the driving unit is connected to the third port of the first sample collection unit. The fourth port of the first sample collection unit is connected to one end of the first pipeline. The other end of the first pipeline is connected to the fifth port of the membrane filtration unit. The sixth port of the membrane filtration unit is connected to one end of the second pipeline. The other end of the second pipeline is connected to the first port of the driving unit. The first liquid level detection unit is disposed on the outer wall of the first pipeline, and the second liquid level detection unit is disposed on the outer wall of the second pipeline. Both the first liquid level detection unit and the second liquid level detection unit are non-contact detection units. By adopting non-contact liquid level detection units and optimizing the pipeline connection structure, direct contact between the sample and mechanical parts is avoided and the fluid shear effect is reduced, thereby effectively inhibiting protein aggregation and precipitation. This effectively reduces protein aggregation and precipitation and improves the accuracy and reliability of sample processing. Attached Figure Description

[0015] Figure 1 This is a schematic diagram of a complete hydraulic circuit system provided for this application.

[0016] Figure 2 A schematic diagram of a complete machine (single sampling unit only) is provided for this application.

[0017] Figure 3 A schematic cross-sectional view of an ultrasonic liquid level sensor (sound field liquid level detection) provided in this application installed on the outer wall of a pipeline. Figure 1 .

[0018] Figure 4 A schematic cross-sectional view of an ultrasonic liquid level sensor (sound field liquid level detection) provided in this application installed on the outer wall of a pipeline. Figure 2 .

[0019] Figure 5 A schematic diagram of the complete machine (including two sampling units) is provided for this application.

[0020] Figure 6 A cross-sectional view of a sampling unit provided in this application.

[0021] Figure 7 This is a schematic diagram of an air filtration device installed at an atmospheric pressure port, as provided in this application.

[0022] Figure 8 This is a schematic diagram of the hydraulic circuit arrangement of a drive unit provided in this application.

[0023] In the diagram: 1. First pipeline; 2. Second pipeline; 3. Third pipeline; 4. Fourth pipeline; 5. First sampling unit; 6. Second sampling unit; 7. First liquid level detection unit; 8. Second liquid level detection unit; 9. Drive unit; 10. Membrane filtration unit; 11. First port; 12. Second port; 13. Third port; 14. Fourth port; 15. Fifth port; 16. Sixth port; 17. Seventh port; 18. Eighth port; 19. Sealing device; 20. Air filtration device; 21. One-way pump; 22. First three-way valve; 23. Second three-way valve; 24. Third three-way valve; 25. Three-way connector. Detailed Implementation

[0024] The technical solutions of this application will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are merely some embodiments of this application, and not all embodiments. The components of this application described and shown in the accompanying drawings can generally be arranged and designed in various different configurations. Therefore, the following detailed description of the embodiments of this application provided in the accompanying drawings is not intended to limit the scope of the claimed application, but merely to illustrate selected embodiments of this application. All other embodiments obtained by those skilled in the art based on the embodiments of this application without inventive effort are within the scope of protection of this application.

[0025] It should be noted that similar reference numerals and letters in the following figures indicate similar items; therefore, once an item is defined in one figure, it does not need to be further defined and explained in subsequent figures. Furthermore, in the description of this application, terms such as "first," "second," etc., are used only to distinguish descriptions and should not be construed as indicating or implying relative importance.

[0026] In biomedical research and clinical diagnosis, the separation and purification of proteins play a crucial role in disease screening, drug development, and the elucidation of biological mechanisms. However, in traditional liquid-phase biological sample handling and transport processes, the membranes of pumps and valves and their complex internal structures are prone to protein aggregation and precipitation, as well as continuous biochemical reactions. These effects or behaviors can affect the accuracy and effectiveness of separation and purification and need to be avoided.

[0027] In this regard, such as Figure 1 As shown, this application proposes a protein solution processing device, which includes a first pipeline, a second pipeline, a first sample collection unit, a first liquid level detection unit, a second liquid level detection unit, a drive unit, and a membrane filtration unit. The drive unit is configured to have a first port and a second port, the first sample collection unit is configured to have a third port and a fourth port, and the membrane filtration unit is configured to have a fifth port and a sixth port. The second port of the drive unit is connected to the third port of the first sample collection unit, the fourth port of the first sample collection unit is connected to one end of the first pipeline, the other end of the first pipeline is connected to the fifth port of the membrane filtration unit, the sixth port of the membrane filtration unit is connected to one end of the second pipeline, and the other end of the second pipeline is connected to the first port of the drive unit. Furthermore, the first liquid level detection unit is disposed on the outer wall of the first pipeline, and the second liquid level detection unit is disposed on the outer wall of the second pipeline; both the first and second liquid level detection units are non-contact detection units.

[0028] For ease of understanding, the following explains some key terms in this embodiment: Protein liquid processing equipment is designed for transporting, separating, and purifying liquid samples containing proteins to obtain the target protein or remove impurities.

[0029] The first and second conduits form the channels of the fluid loop, used to carry and transport the protein solution. These conduits are typically designed with specific inner diameters and wall thicknesses to accommodate the fluid transport requirements.

[0030] The first sample unit is configured to receive the protein sample to be processed and introduce it into the fluid loop of the processing device. This unit typically has a certain volume for storing the initial sample.

[0031] The first and second liquid level detection units are used to monitor the liquid level of the protein solution in the first and second pipelines in real time. These detection units are installed on the outer wall of the pipelines to avoid direct contact with the protein solution.

[0032] A drive unit is used to provide the power required for fluid transport, such as by generating a pressure difference or flow rate, to drive the protein solution to circulate throughout the fluid loop of the device.

[0033] A membrane filtration unit is used to separate or purify protein solutions. This unit typically contains a filter membrane or other separation medium that uses physical or chemical action to retain the target protein or remove impurities.

[0034] Non-contact detection units are sensors that perform detection without direct contact with the medium being tested. By eliminating the need for direct contact with liquids, they avoid problems such as equipment damage and difficulty in cleaning caused by liquid corrosion, contamination, or viscosity. They are insensitive to changes in the viscosity and density of the medium and are suitable for various sample liquids. Especially in protein solution processing, this detection method effectively avoids contamination or alteration of the protein solution's properties.

[0035] like Figure 2 As shown, the protein solution processing device of this embodiment comprises a first pipeline, a second pipeline, a first sample collection unit, a first liquid level detection unit, a second liquid level detection unit, a drive unit, and a membrane filtration unit. These components work together to form a complete fluid processing system. For example, the first and second pipelines can be made of materials such as polytetrafluoroethylene or polyetheretherketone to ensure smooth fluid delivery. The first sample collection unit can be a simple liquid storage container for holding the protein solution to be processed. The drive unit can be a peristaltic pump or a syringe pump for providing fluid power. The membrane filtration unit can be a filter with a microporous membrane for separating proteins.

[0036] The drive unit is configured to have a first port and a second port, which are interfaces for fluid inlet and outlet. For example, the drive unit could be a pump with two independent fluid channels, each corresponding to one port.

[0037] The first sample unit is configured with a third port and a fourth port for connection to external tubing. For example, the third port can serve as an inlet for the driving gas, and the fourth port as an outlet for the protein solution.

[0038] The membrane filtration unit is configured to have a fifth port and a sixth port for fluid inflow and outflow. For example, the fifth port can serve as the inlet for protein solution to enter the membrane filtration unit, and the sixth port as the outlet for a portion of the protein solution after it has passed through the membrane filtration unit. The membrane filtration unit may also include an outlet for filtered liquid to flow out of the membrane filtration unit.

[0039] Regarding the fluid circuit connection, the second port of the drive unit is connected to the third port of the first nano-sample unit. Thus, the drive unit can push or draw fluid into the first nano-sample unit, and can also push gas into the first nano-sample unit and use the gas to drive the liquid out of the first nano-sample unit.

[0040] Furthermore, the fourth port of the first nanosample unit is connected to one end of the first conduit. This allows the protein solution in the first nanosample unit to be delivered to the first conduit.

[0041] Subsequently, the other end of the first conduit is connected to the fifth port of the membrane filtration unit. Thus, the protein solution transported through the first conduit can enter the membrane filtration unit for processing.

[0042] The sixth port of the membrane filtration unit is connected to one end of the second pipeline. This allows the liquid treated by the membrane filtration unit to enter the second pipeline.

[0043] Finally, the other end of the second pipeline is connected to the first port of the drive unit. This forms a complete closed-loop fluid circuit, allowing the protein solution to circulate within the device or flow bidirectionally in both directions, enabling continuous processing.

[0044] Furthermore, the protein solution does not flow through the first and second ports, avoiding direct contact between the sample and mechanical components and reducing fluid shear effects, thereby effectively inhibiting protein aggregation and precipitation, and improving the accuracy and reliability of sample processing.

[0045] like Figure 3 As shown, in order to monitor the liquid level in the pipeline in real time, a first liquid level detection unit is installed on the outer wall of the first pipeline. For example, this detection unit can be a capacitive liquid level sensor, which determines the liquid level by sensing changes in the electric field outside the pipe wall.

[0046] like Figure 3 and Figure 4 As shown, similarly, a second liquid level detection unit is installed on the outer wall of the second pipeline to monitor the liquid level in the second pipeline. For example, this detection unit can also be an optical liquid level sensor, which determines the liquid level by detecting changes in the refraction or reflection of light in the medium inside and outside the pipe wall.

[0047] In a preferred embodiment, both the first and second liquid level detection units are non-contact detection units. This means that the detection process does not introduce any physical probes or components into direct contact with the protein solution, thereby avoiding potential contamination, protein adsorption, or alteration of biological activity, and significantly reducing protein aggregation caused by the shear forces of the reciprocating motion of the liquid. For example, sensors based on ultrasonic, infrared, or electromagnetic induction principles can be used as non-contact detection units.

[0048] This device achieves controlled transport and processing of protein solutions by constructing a closed-loop fluid circuit consisting of a drive unit, a sample collection unit, a membrane filtration unit, and tubing. This design effectively reduces fluid retention and shearing within the complex pump and valve structure, thereby lowering the risk of protein aggregation and precipitation. Simultaneously, a non-contact liquid level detection unit is installed on the outer wall of the tubing, preventing the detection probe from directly contacting the protein solution. This eliminates contamination or protein adsorption caused by contact, ensuring zero interference with the protein solution properties during the detection process, thus improving the accuracy and effectiveness of protein separation and purification.

[0049] In some of the embodiments described above in this application, a first liquid level detection unit and a second liquid level detection unit are proposed to achieve non-contact detection of the liquid level in the pipeline of the protein liquid processing device. However, in practical applications, if the response speed of the liquid level detection unit cannot match the dynamic process of protein liquid transportation, or if the detection mechanism has insufficient ability to identify different media states, it will lead to liquid level monitoring delay or misjudgment, thereby affecting the accuracy and safety of protein liquid processing.

[0050] In this regard, this application further proposes that both the first liquid level detection unit and the second liquid level detection unit are acoustic field liquid level detection units, and / or, the response time of the acoustic field liquid level detection unit during air detection is less than 10ms, and / or, the response time of the acoustic field liquid level detection unit during liquid detection is less than 1s.

[0051] Specifically, an acoustic field liquid level detection unit is a device that detects the presence and position of a liquid by utilizing the differences in the propagation characteristics of sound waves in different media. Its working principle typically involves emitting sound waves and receiving reflected or transmitted sound waves, determining the medium type by analyzing the changes in characteristics (e.g., sound velocity, attenuation, phase, or frequency shift) produced when the sound waves propagate in air and liquid. For example, ultrasonic liquid level detection technology can be used, emitting high-frequency ultrasonic waves through a piezoelectric transducer and identifying the liquid level based on the differences in reflected or transmitted signals at the interface between the pipe wall and the internal medium. Another approach utilizes the principle of acoustic resonance, generating acoustic resonance by exciting the pipe or its internal cavity. When the medium inside the pipe changes from air to liquid, the system's resonant frequency or damping characteristics change significantly, thus achieving liquid level detection. The non-contact detection characteristic of the acoustic field liquid level detection unit effectively avoids direct contact with the protein liquid, thereby eliminating the risk of cross-contamination and preventing interference with the physicochemical properties of the protein liquid.

[0052] Here, the ultrasonic liquid level sensor is mainly used to monitor the "dryness" and "wetness" of the pipeline. Therefore, the ultrasonic liquid level sensor is also a dryness and wetness sensor. It has a pair of transceiver probes outside the pipe. When the ultrasonic wave passes through the liquid: strong transmission, large receiving signal → "wet / liquid present". When encountering bubbles / air: the gas-liquid acoustic impedance difference is extremely large, the sound wave is almost totally reflected / strongly scattered, and the receiving signal drops sharply → "dry / air present". "Dry → Wet" (air inlet → liquid inlet): the process is as follows: initially "dry": air in the pipe, ultrasonic waves can hardly pass through, receiving signal ≈ 0. Once liquid arrives, it instantly fills the pipeline, and the sound wave immediately changes from "total reflection" to "high transmission". Signal change: a sudden jump from 0 to full amplitude, the threshold is easily determined, and there is almost no lag. "Wet → Dry" (liquid inlet → air inlet): the process is as follows: initially "wet": full pipe of liquid, receiving signal is stable and high. When bubbles first arrive: local crowding, liquid film residue, discontinuous bubbles; the ultrasonic wave does not immediately stop completely, but gradually attenuates and vibrates. During the transition phase, liquid adheres to the tube wall / probe surface, and the liquid film evaporates / sheds slowly; bubbles grow from small to large and from scattered to continuous, causing the signal to slowly decline and fluctuate; the circuit needs to de-jitter, filter, and perform multiple sampling confirmations to prevent false alarms. Only when it is completely "dry": the liquid film completely disappears, air becomes continuous, and the signal drops to 0.

[0053] To further ensure the system's rapid response to changes in the state of the medium within the pipeline, this application specifies that the response time of the acoustic field liquid level detection unit for air detection is less than 10 ms. This means that when air is present in the pipeline (e.g., pipeline purging, bubble generation, or air resistance formation), the detection unit can identify the presence of air in an extremely short time (milliseconds). Achieving this rapid response typically requires high-frequency acoustic wave transmission and reception, optimized signal processing algorithms, and a high-performance processor to ensure that the acoustic signal can propagate, be captured, and analyzed rapidly.

[0054] Meanwhile, to ensure stable and timely monitoring of the liquid state, this application limits the response time of the acoustic field liquid level detection unit to less than 1 second during liquid detection. This response time ensures that the detection unit can promptly capture liquid level information when the protein liquid flows or the liquid level changes. Achieving this response time typically requires balancing the signal sampling frequency with the complexity of data processing, especially when dealing with protein liquids that may contain air bubbles or have a certain viscosity. In such cases, signal averaging or filtering may be necessary to improve the accuracy and stability of the detection.

[0055] Through the above technical solutions, the protein liquid processing device proposed in this application can significantly improve the accuracy and safety of liquid level detection. The introduction of the acoustic field liquid level detection unit overcomes the interference and contamination problems of traditional contact sensors on protein liquid flow, and also solves the limitation of optical sensors in inaccurate detection in non-transparent pipelines or gas-liquid two-phase flows (such as protein liquid containing bubbles). Since the propagation characteristics of sound waves in different media are much greater than those of light waves, acoustic field detection can accurately locate the liquid level without extremely high sampling frequencies, which is especially suitable for gas-liquid two-phase fluids that may be generated during the membrane filtration unit processing.

[0056] Specifically, the response time of the acoustic field liquid level detection unit during air detection is limited to less than 10ms, enabling the system to respond to anomalies such as pipeline purging, air bubbles, or air resistance in milliseconds. This rapid response capability is crucial for preventing damage caused by the drive unit idling, avoiding transport interruptions due to air resistance, and timely adjustment of the transport strategy, thereby effectively ensuring the continuity of the protein liquid processing process and the safe operation of the equipment.

[0057] Furthermore, by limiting the response time of the acoustic field liquid level detection unit to less than 1 second, the system can stably and promptly track the liquid level during protein liquid transport. This is crucial for accurately controlling the volume of the protein liquid, preventing overflow or drying, and maintaining accurate level control when handling high-viscosity or easily sedimented protein liquids. Through precise control of the air and liquid detection response times, the protein liquid processing device of this application can more effectively adapt to the dynamic process of protein liquid transport, avoiding the impact on processing accuracy due to detection lag or misjudgment, thereby comprehensively improving the reliability and efficiency of protein liquid processing.

[0058] In some embodiments described above in this application, a pipeline connection structure for a protein liquid processing device is proposed. However, in practical applications, if the pipeline is made of a transparent material, the light from the optical sensor may induce a photochemical reaction in the protein liquid or cause denaturation of photosensitive proteins. Furthermore, if the pipeline material is not biologically inert, the protein liquid is prone to non-specific adsorption or chemical reaction with the pipeline wall during transport, which may lead to protein aggregation, precipitation, or loss of activity, affecting the accuracy and effectiveness of separation and purification.

[0059] In this regard, this application further proposes that the materials of the first pipeline and the second pipeline are both non-transparent materials.

[0060] Specifically, opaque materials refer to materials that do not allow light to pass through. Their main function is to block external light from entering the tubing, thereby protecting the protein solution flowing inside from light exposure. Light, especially specific wavelengths of ultraviolet and visible light, can cause photochemical reactions in proteins, such as oxidation, cross-linking, or conformational changes, leading to protein denaturation, aggregation, or loss of activity. Various materials can be used to achieve opacity; for example, by adding opaque pigments or fillers to the tubing material, or by using materials that are inherently opaque. Common opaque materials include, but are not limited to: black polyetheretherketone (PEEK), opaque polypropylene (PP), opaque polyethylene (PE), and opaque polytetrafluoroethylene (PTFE).

[0061] In this regard, this application further proposes that the materials of the first pipeline and the second pipeline are both biologically inert materials.

[0062] Meanwhile, bio-inert materials refer to materials that do not readily undergo physical adsorption, chemical reactions, or biodegradation when in contact with biomolecules (such as proteins). Their core function is to reduce non-specific interactions between the protein solution and the tube wall during transport, thereby preventing protein adsorption, aggregation, precipitation, or loss of activity on the tube wall, ensuring the integrity and purity of the protein solution. The selection of bio-inert materials is usually based on their surface chemical properties and structure. For example, materials with low surface energy, high chemical stability, and smooth surfaces typically exhibit good bio-inertness. Common bio-inert materials include, but are not limited to: polyetheretherketone (PEEK), polytetrafluoroethylene (PTFE), polypropylene (PP), and polyethylene (PE).

[0063] By using the aforementioned technical solution, the materials of the first and second tubing are limited to non-transparent materials, effectively blocking external light from irradiating the protein solution inside the tubing. This prevents light-induced protein denaturation, aggregation, or photochemical reactions, ensuring the structural stability and bioactivity of the protein solution during transport. Simultaneously, using a bio-inert material as the tubing material significantly reduces non-specific adsorption and chemical reactions between protein molecules and the tubing wall, effectively preventing protein aggregation, precipitation, or loss of activity on the tubing wall, thus guaranteeing the purity and integrity of the protein solution throughout the entire processing. This dual material optimization improves the accuracy and reliability of protein solution processing from both physical and chemical perspectives, providing high-quality samples for subsequent protein separation, purification, and analysis.

[0064] In some of the embodiments described above in this application, a sound field liquid level detection unit is proposed to achieve non-contact detection of the liquid level in the pipeline of the protein liquid processing device. However, in practical applications, due to the special nature of the pipeline material and the high requirements for detection accuracy and safety, how to ensure that the sound field detection maintains high sensitivity under low energy radiation and effectively distinguishes the response differences between air and liquid media to avoid misjudgment or detection lag has become a key challenge to improve the reliability of the device.

[0065] Furthermore, both the first and second tubing are made of PEEK. PEEK (polyetheretherketone) is particularly suitable for processing protein-containing liquids, primarily due to its bioinertness, low adsorption, lack of metal ion leaching, resistance to aqueous phases / buffers, and sterilizability, which maximizes the protection of protein activity and recovery rate. Its extremely low protein adsorption, ultra-smooth inner wall (the inner wall roughness Ra of precision-extruded PEEK tubing is <0.1μm, far lower than ordinary plastics, reducing physical adsorption and deposition of proteins), and hydrophobic / hydrophilic balance (its surface is weakly hydrophobic, resulting in extremely low adsorption of most water-soluble proteins; compared to PTFE, it does not easily generate hydrophobic adsorption; compared to stainless steel, it has almost no electrostatic adsorption) are all highly beneficial for protein solution processing. Therefore, the protein solution flows stably, is less prone to eddies and localized excessive concentrations, and avoids protein aggregation.

[0066] In this regard, this application further proposes that the ultrasonic intensity Ispta of the acoustic field liquid level detection unit be less than 100 mW / cm. 2 .

[0067] Among them, the ultrasonic intensity (i.e., spatial peak temporal average intensity, Ispta) of the acoustic field liquid surface detection unit is an important parameter for measuring ultrasonic energy radiation, and its value is less than 100mW / cm². 2 The aim is to ensure that the energy radiation of ultrasound to the protein solution is kept at an extremely low level. For protein solution processing, excessively high ultrasound intensity may cause changes in protein molecular structure, aggregation, or precipitation, thereby affecting the bioactivity of the protein solution and the effectiveness of subsequent processing. Limiting it to a low level aims to protect the integrity of the protein solution. One approach is to precisely control the driving voltage and current of the ultrasonic transducer inside the acoustic field liquid level detection unit to ensure that the output ultrasonic energy is limited to a preset low intensity range at the transmitting end. For example, a low-power piezoelectric ceramic transducer can be used, along with a specially designed low-power drive circuit. Another approach is to optimize the coupling medium and coupling method between the ultrasonic transducer and the pipeline, such as using a gel or liquid with well-matched acoustic impedance as a coupling agent, and adjusting the distance between the transducer and the outer wall of the pipeline to ensure that the effective intensity Ispta of the ultrasound can be maintained at less than 100 mW / cm² when it enters the pipeline.2 The threshold is below the limit, while ensuring sufficient penetration for detection.

[0068] In this regard, this application further proposes that the response time of the acoustic field liquid level detection unit during liquid detection is greater than or equal to 10 times the response time of the acoustic field liquid level detection unit during air detection.

[0069] Meanwhile, the response time of the acoustic field liquid level detection unit during liquid detection is greater than or equal to 10 times that during air detection. Response time refers to the time required for the acoustic field liquid level detection unit to output a corresponding detection result from receiving a change in the ultrasonic signal. Air and liquid exhibit significant differences in the propagation characteristics of ultrasonic waves (such as sound velocity and attenuation), causing the detection unit to produce different signal responses when encountering air and liquid. By setting the liquid detection response time to be much longer than the air detection response time, this difference can be utilized for more robust medium discrimination. One implementation method is to set different signal integration or averaging time thresholds in the signal processing module of the acoustic field liquid level detection unit. For example, for detected air signals, a short period of signal stability is sufficient to classify it as air; while for liquid signals, a longer period of sustained signal stability or consistent sampling results are required to classify it as liquid, thus achieving differentiation in response time at the software level. Another implementation method is to combine hardware filtering and software algorithms. At the hardware level, filters with different time constants can be designed to distinguish between rapidly changing air signals and relatively stable liquid signals. At the software level, algorithms such as state machines or Bayesian discrimination can be introduced, requiring the signal characteristics of the liquid state to continuously meet certain conditions (e.g., N consecutive sampling points indicate the presence of liquid) before triggering the liquid detection result, while the judgment conditions for the air state are relatively relaxed, thereby achieving a proportional relationship between response time.

[0070] Through the above technical solution, this application achieves gentle and non-destructive detection of protein liquids in the application of the acoustic field liquid level detection unit, and significantly improves the accuracy and robustness of liquid level determination. Specifically, by limiting the ultrasonic intensity (Ispta) of the acoustic field liquid level detection unit to less than 100 mW / cm2, biological damage such as denaturation, aggregation, or precipitation that high-intensity ultrasonic waves may cause to the protein liquid is effectively avoided, ensuring the biological activity and integrity of the protein liquid during processing. This is particularly crucial for non-contact detection when the first and second pipelines are made of non-transparent and bio-inert materials, solving the problem that traditional detection methods may damage the protein liquid. Simultaneously, by setting the response time of the acoustic field liquid level detection unit for liquid detection to be greater than or equal to 10 times its response time for air detection, this application establishes an intelligent medium discrimination mechanism. This mechanism utilizes the inherent differences in the propagation characteristics of ultrasonic waves in air and liquid, combined with a time threshold for judgment, enabling the system to effectively distinguish between the actual liquid state in the pipeline and interference signals such as instantaneous bubbles and liquid surface fluctuations. This design avoids misjudgments caused by instantaneous signal changes, ensuring the stability and reliability of liquid level detection results, thereby improving the automation level and operational safety of the entire protein liquid processing device. Its effect is particularly significant in scenarios where precise control of the liquid level position is required to avoid drowsy suction or overflow.

[0071] In some of the solutions described above in this application, a first pipeline and a second pipeline are proposed for transporting protein solution. However, in the actual fluid transport process, the geometric parameters of the pipeline directly affect the fluid flow resistance, shear stress, and accuracy of liquid level detection. If the pipeline wall thickness and diameter are not properly designed, it can easily lead to low fluid transport efficiency, pipeline deformation affecting detection accuracy, or even protein structure damage or aggregation due to excessive shear force.

[0072] In this regard, this application further proposes that the wall thickness of the first pipeline and the second pipeline is 8%-30% of their outer diameter.

[0073] Specifically, the wall thickness of the first and second pipes is 8%-30% of their outer diameter. This wall thickness ratio is designed to ensure sufficient mechanical strength of the pipes when subjected to internal fluid pressure, preventing deformation caused by pressure fluctuations or external stress, thereby maintaining the stability of the pipe geometry. At the same time, appropriate wall thickness also ensures a certain degree of flexibility in the pipes, which is crucial for signal penetration in non-contact liquid level detection units (such as acoustic liquid level detection units). Excessively thick walls will significantly attenuate the detection signal, while excessively thin walls may result in insufficient strength. For example, high-molecular materials such as polytetrafluoroethylene (PTFE) or polyetheretherketone (PEEK) can be used, manufactured through precision extrusion molding, precisely controlling the ratio of wall thickness to outer diameter; alternatively, hard materials such as glass or quartz can be used, formed through precision stretching or sintering processes, with the ratio of wall thickness to outer diameter also strictly controlled within a specified range to balance strength and the transmission efficiency of the detection signal.

[0074] In this regard, this application further proposes that the inner diameter of both the first pipeline and the second pipeline is greater than or equal to 0.5 mm.

[0075] Furthermore, the inner diameter of both the first and second conduits is greater than or equal to 0.5 mm. This inner diameter limitation is primarily intended to reduce flow resistance during fluid transport within the conduits, decrease pumping energy consumption, and effectively reduce shear force between the fluid and the conduit wall. For protein solutions, excessive shear force can lead to protein denaturation, aggregation, or loss of activity. Therefore, increasing the inner diameter to reduce shear stress is crucial for maintaining the biological activity of the protein solution. For example, during conduit manufacturing, the inner diameter can be ensured to reach or exceed 0.5 mm by selecting appropriate mold sizes or mandrel diameters; alternatively, for integrated conduits in microfluidic chips, the width and depth of the flow channels can be precisely controlled using microfabrication techniques such as photolithography, wet etching, or dry etching to ensure that the equivalent inner diameter meets this requirement.

[0076] In this regard, this application further proposes that the outer diameter of the first pipeline is less than or equal to 5 mm, and / or the outer diameter of the second pipeline is less than or equal to 5 mm.

[0077] Furthermore, the outer diameter of the first pipeline is less than or equal to 5 mm, and / or the outer diameter of the second pipeline is less than or equal to 5 mm. Limiting the pipeline outer diameter to a smaller range helps reduce the overall volume of the protein liquid processing device, facilitating integrated and miniaturized design and improving space utilization. On the other hand, a smaller outer diameter optimizes the coupling distance between the pipeline and the non-contact liquid level detection unit, allowing the signal emitted by the detection unit (such as the acoustic liquid level detection unit) to penetrate the pipe wall more efficiently and accurately identify the liquid level position inside the pipe, improving detection sensitivity and accuracy. For example, the outer diameter of the pipeline can be controlled within 5 mm through precision extrusion or stretching processes to meet the design requirements of compact equipment; or, in integrated designs, micro-connectors and encapsulation technologies can be used to ensure that the external dimensions of the pipeline meet requirements while facilitating a tight fit with the non-contact liquid level detection unit.

[0078] Through the above technical solution, this application effectively solves the problems of high flow resistance, high shear force, easy deformation of pipelines, and inaccurate liquid level detection during protein solution transportation by precisely limiting the geometric parameters of the first and second pipelines. Specifically, the pipeline wall thickness is set to 8%-30% of its outer diameter. This ensures that the pipeline has sufficient mechanical strength to resist driving pressure and prevent deformation, while also taking into account the good penetration of the pipeline wall for non-contact liquid level detection signals. This allows the first and second liquid level detection units to stably and accurately acquire liquid level information within the pipeline. At the same time, limiting the inner diameter of the pipeline to greater than or equal to 0.5 mm significantly reduces the flow resistance of the protein solution in the pipeline and reduces shear stress during transportation. This effectively prevents protein denaturation, aggregation, or reduced activity due to mechanical shearing, thus ensuring the biological activity and purity of the protein solution. Furthermore, limiting the outer diameter of both the first and second pipelines to 5 mm or less not only facilitates the miniaturization and integration of the device, but more importantly, optimizes the coupling relationship between the pipelines and the non-contact liquid level detection unit. This allows the detection signal to act on the liquid surface inside the pipeline more efficiently and accurately, further improving the accuracy and reliability of liquid level detection. The synergistic optimization of these parameters collectively creates a low-resistance, low-shear, and high-accuracy protein solution delivery environment, ensuring the stability and processing effect of the protein solution throughout the entire process.

[0079] In some of the embodiments described above in this application, a closed-loop processing system consisting of a first sampling unit, a first pipeline, a membrane filtration unit, a second pipeline, and a drive unit is proposed to realize the transport and processing of protein solutions. However, in this process, since the system only has a single sampling unit, when processing large-scale samples or requiring multi-stage cyclic processing, the volume limitation of the single sampling unit and the insufficient flexibility of flow path switching result in the inability to efficiently perform continuous sample processing or multi-component switching, thus limiting the application efficiency and flexibility of the device in complex biological sample processing scenarios.

[0080] In this regard, this application further proposes that the protein liquid processing device also includes a second sample unit, which includes a seventh port and an eighth port. The other end of the second pipeline is connected to the seventh port of the second sample unit, and the eighth port of the second sample unit is connected to the first port of the drive unit.

[0081] Among them, such as Figure 5 As shown, the second sampling unit is a container used for storing, buffering, or processing protein solutions. Its design aims to provide additional sample processing capacity and flow path flexibility to compensate for the limitations of a single sampling unit when handling complex or large-scale samples. This second sampling unit can be a stand-alone reservoir, a replaceable sample vial, a cavity with a piston or diaphragm, or a specific volume space integrated within the main body of the device. Its material is typically bio-inert to avoid unnecessary chemical reactions or adsorption with the protein solution, ensuring the biological activity and purity of the protein solution.

[0082] More importantly, with the second nano-sample unit, the liquid system has a buffer container, which can support rapid forward and reverse driving in the early stage of processing to quickly concentrate the protein solution initially; while in the later stage of processing, the subsequent bidirectional co-drive step can be used for bidirectional extrusion to further concentrate the residual substances and achieve better enrichment and purification results.

[0083] The seventh and eighth ports are fluid interfaces on the second nano-sampling unit, used to connect to the external piping and the drive unit, respectively. The seventh port, as the inlet of the second nano-sampling unit, is typically connected to the other end of the second piping, receiving fluid processed by the membrane filtration unit. The eighth port, as the outlet of the second nano-sampling unit, is typically connected to the first port of the drive unit, delivering the fluid from the second nano-sampling unit to the drive unit. These ports can be standardized connectors, such as Luer joints, threaded interfaces, or quick couplings, to ensure reliable connections and tight seals.

[0084] The other end of the second pipeline connects to the seventh port of the second nano-sampling unit, and the eighth port of the second nano-sampling unit connects to the first port of the drive unit. These connections together form a new fluid pathway. Specifically, the second nano-sampling unit is connected in series between the second pipeline and the first port of the drive unit, so that after the fluid passes through the membrane filtration unit and the second pipeline, it first enters the second nano-sampling unit and is then transported to the drive unit. This connection method allows the second nano-sampling unit to serve as an important node in the fluid circulation path, enabling temporary storage, diversion, or further processing of the fluid.

[0085] Through the above technical solution, this application introduces a second nano-sample unit on the basis of the original closed-loop processing system, and cleverly connects it in series between the second pipeline and the first port of the drive unit, thereby constructing a cyclic processing architecture with dual nano-sample units. This design significantly improves the flexibility of the device's flow path configuration and sample processing capability. The addition of the second nano-sample unit enables the system to achieve bidirectional or multidirectional sample storage and buffering, effectively solving the problems of volume limitations and insufficient flow path switching flexibility of a single nano-sample unit when processing large-scale samples or requiring multi-stage cyclic processing. The drive unit can now more flexibly control the reciprocating transport of fluid between the first and second nano-sample units through its first and second ports, thereby supporting more complex processing flows, such as continuous filtration, sample dilution, multi-component mixing, or alternating processing of different samples. This optimization not only avoids fluid stagnation in the pipeline, but also provides a physical basis for subsequent implementation of multi-stage filtration, sample dilution, or multi-component mixing, greatly improving the application efficiency and flexibility of the device in complex biological sample processing scenarios.

[0086] In some of the solutions described above in this application, a bidirectional drive of liquid in both forward and reverse directions is proposed to form a tangential flow on the surface of the filter membrane in the membrane filtration unit, which effectively suppresses the excessive accumulation of particles on the membrane surface.

[0087] In this regard, this application further proposes that when the first liquid level detection unit is triggered for the second time, the forward movement of the liquid is stopped.

[0088] Through the above technical solution, this application introduces a dynamic motion termination mechanism based on the trigger state of the liquid level detection unit, which effectively improves the filtration efficiency of the membrane filtration unit. Specifically, for example, during the forward movement of liquid, when liquid flows from the first nano-sample unit to the membrane filtration unit, the first liquid level detection unit will be triggered for the first time (changing from the original liquid-free state to the liquid-containing state). If the liquid continues to flow to the membrane filtration unit and then to the second nano-sample unit, when all the liquid has flowed through the first liquid level detection unit, it will trigger the first liquid level detection unit a second time (changing from a liquid-containing state to a liquid-free state). This indicates that all the liquid has flowed through the first liquid level detection unit, at which point the forward movement is stopped (and the subsequent reverse movement begins). Some liquid remains in the membrane filtration unit and pipeline, reducing the amount of liquid adhering to the second nano-sample unit and making more effective use of the membrane filtration unit's filtration capacity. Otherwise, if all the remaining unfiltered liquid is allowed to flow to the second nano-sample unit, the membrane filtration unit will have a long period of unfiltered liquid, which will reduce the filtration efficiency and make the filter cake layer attached to the membrane filtration unit more firmly attached, making it more difficult to be washed away by the reverse movement, thus reducing the subsequent filtration flux.

[0089] In this regard, this application further proposes that when the second liquid level detection unit is triggered for the second time, the reverse movement of the liquid is stopped.

[0090] The same technical principle applies to the reverse motion. Therefore, by monitoring the number of triggers of the liquid level detection unit, the system can determine whether the current filtration step needs to be stopped to avoid unnecessary energy consumption or further sedimentation. This closed-loop control strategy, through real-time feedback of liquid level information and judgment based on the time dimension, significantly improves the automation control accuracy, system robustness, and safety of the particulate filtration process, ensuring efficient and stable operation under complex fluid conditions.

[0091] In some of the solutions described above in this application, a liquid level detection unit is proposed to monitor the liquid level position in the pipeline. However, during the protein liquid processing, due to the complex fluid dynamics behavior in the pipeline, if the installation position of the liquid level detection unit is not set properly, the detection signal is easily affected by fluid disturbance, residual bubbles or liquid level fluctuations at the pipeline connection, thereby reducing the accuracy and stability of liquid level detection and thus affecting the precision of protein liquid processing.

[0092] In this regard, this application further proposes that the length of the pipeline from the detection point of the first liquid level detection unit to the end of the first pipeline connected to the first nano-sample unit is greater than or equal to three times the length of the pipeline from the detection point to the end of the first pipeline connected to the membrane filtration unit.

[0093] Specifically, the technical features of the first liquid level detection unit—the distance from its detection point to the end of the first pipeline connecting to the first sampling unit, and the distance from its detection point to the end of the first pipeline connecting to the membrane filtration unit—define the specific installation position of the first liquid level detection unit on the first pipeline, quantified by measuring the distance from its detection point to the connection points at both ends of the pipeline. The pipeline length refers to the distance measured along the centerline of the pipeline. This quantification of distance provides a basis for precise installation and positioning. In practice, this can be achieved by pre-setting marker points during the pipeline design phase, or by using measuring tools (such as tape measures or laser rangefinders) during actual installation for precise measurement and positioning. Another approach is to utilize an automated assembly system, using pre-programmed coordinates or sensor feedback to ensure the precise installation of the detection unit.

[0094] The requirement that the distance from the detection point to one end of the first pipeline connecting to the membrane filtration unit be greater than or equal to three times the length of the pipeline itself defines the asymmetrical installation ratio of the detection point of the first liquid level detection unit relative to the connection points at both ends of the first pipeline. Specifically, the detection point should be closer to one end of the membrane filtration unit, and its distance to one end of the first nano-sample unit should be at least three times the distance to that end. This ratio aims to position the detection point in a region of relatively stable hydrodynamic behavior, away from the nano-sample unit connection points where significant disturbances may occur. During pipeline design, the detection point location satisfying this ratio can be calculated based on the total pipeline length and the dimensions of the membrane filtration unit. During manufacturing and assembly, pipeline assemblies with graduations or positioning grooves can be used, or a visual recognition system can be used to assist in positioning to ensure that the detection unit is installed in a position that meets this ratio requirement.

[0095] In this regard, this application further proposes that the distance from the detection point of the second liquid level detection unit to the end of the second pipeline connected to the second nano-sample unit is greater than or equal to three times the distance from the detection point to the end of the second pipeline connected to the membrane filtration unit.

[0096] The distance from the detection point of the second liquid level detection unit to the end of the second pipeline connecting to the second sampling unit is greater than or equal to three times the distance from the detection point to the end of the second pipeline connecting to the membrane filtration unit. This feature is similar to the arrangement of the first pipeline, ensuring that the detection point of the second liquid level detection unit on the second pipeline also follows the same asymmetric installation principle, i.e., closer to the membrane filtration unit end, and the distance to the second sampling unit end is at least three times the distance to the membrane filtration unit end. This guarantees high accuracy and stability of liquid level detection on both pipelines in the entire protein solution processing device. Similar to the first pipeline, this can be achieved through design specifications, prefabricated components, or automated assembly technology. For example, a modular design can be adopted, in which the installation positions of pipeline sections and detection units are pre-fixed to ensure that geometric proportions are met.

[0097] This application effectively optimizes the installation position of the liquid level detection units by setting the detection point of the first liquid level detection unit at a position where the pipe length from the end of the first pipeline connecting to the first nano-sample unit is greater than or equal to three times the pipe length from the end of the first pipeline connecting to the membrane filtration unit, and by setting the detection point of the second liquid level detection unit at a position where the pipe length from the end of the second pipeline connecting to the second nano-sample unit is greater than or equal to three times the pipe length from the end of the second pipeline connecting to the membrane filtration unit. This asymmetrical installation layout allows the detection point to be located away from areas of fluid disturbance, residual air bubbles, or liquid level fluctuations that may occur at the connection between the first and second nano-sample units, thereby ensuring that the non-contact detection unit (such as the acoustic field liquid level detection unit) can perform detection in a pipe section where the fluid flow is relatively stable. Given that the first and second pipelines are made of non-transparent materials, and the liquid level detection unit is a non-contact detection unit, accurate external positioning is crucial for accurately identifying the internal liquid level. By placing the detection point closer to the membrane filtration unit, the actual liquid level changes inside the membrane filtration unit or near its ports can be captured more accurately. This optimization significantly improves the accuracy and stability of liquid level detection, providing a reliable control basis for the protein liquid treatment process. This ensures the precision and effectiveness of protein liquid treatment and avoids problems such as protein aggregation, precipitation, or uncontrolled biochemical reactions caused by inaccurate liquid level detection.

[0098] In some of the solutions described above in this application, a pipeline connection structure for a protein liquid processing device is proposed. However, during the transport of the protein liquid, if the driving medium comes into direct contact with the protein liquid, the pump and valve structure, membrane, and complex flow channels inside the driving unit can easily cause the protein to aggregate, precipitate, or undergo biochemical reactions, thereby seriously affecting the accuracy and effect of separation and purification.

[0099] In response, this application proposes a protein liquid processing device, wherein the driving unit is a gas-driven device.

[0100] Specifically, the drive unit is a gas-driven device, which is a device that uses gas as a working medium to provide power. In the protein liquid processing device, its core function is to provide a non-contact driving method to avoid direct contact between the drive components and the protein liquid. For example, an air pump or compressed gas source can be used, along with a precision air pressure regulating valve and a solenoid valve, to indirectly drive the flow of protein liquid in the pipeline by precisely controlling the gas pressure and flow rate. Alternatively, a pneumatic actuator can be used to drive a piston or diaphragm through air pressure, thereby transmitting pressure to the protein liquid and realizing the delivery of the protein liquid.

[0101] In response, this application proposes a protein liquid processing device, wherein the driving unit is a gas driving device, and the protein liquid does not flow through the first port and the second port.

[0102] Simultaneously, the protein solution does not flow through the first and second ports; here, "protein solution" specifically refers to the protein solution to be processed. This characteristic means that the protein solution will not enter the first and second ports of the drive unit throughout the entire processing, i.e., it will not directly contact the internal mechanical structure of the drive unit. This can be achieved by setting a flexible isolation membrane or gas-liquid interface between the drive unit and the protein solution pipeline. Gas pressure acts on the membrane or gas-liquid interface, thereby propelling the protein solution, while the protein solution itself is isolated outside the drive unit. Another method is that the drive unit uses external gas pressure to act on a deformable container, such as a flexible bag or tube, which contains the protein solution. When gas pressure is applied to the outside of the container, the container deforms and propels the protein solution to flow, while the ports of the drive unit are only connected to the gas.

[0103] Through the above technical solution, this application achieves physical isolation between the driving medium and the protein solution by employing a gas-driven device and ensuring that the protein solution does not flow through the first and second ports of the driving unit. This non-contact driving method fundamentally avoids direct contact between the protein solution and the pump valve structure, membrane, and complex flow channels inside the driving unit. Therefore, it effectively eliminates the shear force, retention effect, and potential biochemical contamination that may be caused to the protein solution by traditional mechanical pumping methods, thereby significantly reducing the risk of protein aggregation, precipitation, or unnecessary biochemical reactions during transport. This ensures the purity and stability of the protein solution flowing throughout the processing device, providing a high-quality sample environment for subsequent membrane filtration, and thus guaranteeing the accuracy and effectiveness of protein separation and purification.

[0104] In some of the embodiments described above in this application, a sample-holding unit is proposed to hold the protein solution. However, if the volume design of the sample-holding unit is not reasonable during the protein solution processing, it may not be able to fully contain the liquid in the pipeline and membrane filtration unit, which may lead to problems such as liquid overflow, pressure fluctuation or incomplete processing during the circulation or processing of the system, thereby affecting the purification efficiency of the protein solution and the stability of the system operation.

[0105] In this regard, this application further proposes that the volume of the first sampling unit is greater than the sum of the volumes of the first pipeline, the second pipeline and the membrane filtration unit.

[0106] The volume of the first nano-sample unit is greater than the sum of the volumes of the first pipeline, the second pipeline, and the membrane filtration unit. This is to ensure that the first nano-sample unit has sufficient storage space to completely accommodate all liquids within the system pipelines (including the first and second pipelines) and the membrane filtration unit. Specifically, the volume can be determined and guaranteed through one or a combination of the following methods: During the design phase, the total internal volume of the first pipeline, the second pipeline, and the membrane filtration unit is accurately calculated, and the internal dimensions of the first nano-sample unit are designed accordingly (e.g., by adjusting its height, diameter, or shape) to make its volume significantly greater than this total; or, during manufacturing, a first nano-sample unit with a predetermined volume is used, and its performance is verified through volume measurement or calibration methods to ensure that it meets the aforementioned volume requirements; or, an adjustable-volume first nano-sample unit can be used, with its internal space adjusted mechanically or electronically to adapt to volume requirements under different pipeline configurations or processing needs.

[0107] In this regard, this application further proposes that the volume of the second sampling unit is greater than the sum of the volumes of the first pipeline, the second pipeline and the membrane filtration unit.

[0108] Meanwhile, the volume of the second nano-sampling unit is greater than the sum of the volumes of the first pipeline, the second pipeline, and the membrane filtration unit. This is designed to provide sufficient storage capacity for the second nano-sampling unit to meet the liquid holding requirements of the system under different operating modes (e.g., when liquid begins to circulate from or flows back to the second nano-sampling unit). In practice, a design and verification method similar to that of the first nano-sampling unit can be adopted: the internal structure and dimensions of the second nano-sampling unit are designed based on the total internal volume of the first pipeline, the second pipeline, and the membrane filtration unit, ensuring that its volume is greater than the sum of these volumes; alternatively, in practical applications, a second nano-sampling unit with a volume meeting the requirements can be selected or configured according to the needs of the processing flow, and verified through appropriate quality control measures; furthermore, a design with interchangeable inner liner or a retractable structure can be adopted, allowing the effective volume of the second nano-sampling unit to be adjusted according to actual needs, ensuring that it is always greater than the total volume of the pipeline and the membrane filtration unit.

[0109] By rationally designing the volume of the first and / or second sample collection units to be greater than the sum of the volumes of the first and second pipelines and the membrane filtration unit through the above technical solution, this device can effectively solve the problems of liquid overflow, pressure fluctuations, and incomplete treatment caused by insufficient volume during protein solution processing. Specifically, when the drive unit performs liquid transport or circulation, such as completely emptying the liquid in the pipelines and membrane filtration unit into the sample collection unit, the sufficient volume of the sample collection unit ensures that all liquid is safely collected, avoiding contamination and loss caused by liquid overflow. In addition, this volume matching design provides the necessary buffer space for the system, which helps stabilize the internal pressure of the system and reduces pressure transients caused by poor liquid transport or sudden stoppage, thereby protecting precision components such as the membrane filtration unit and drive unit. More importantly, ensuring that the sample collection unit can completely contain the liquid in the tubing and membrane filtration unit means that the protein solution can be completely recovered or transferred at the end of each cycle or batch processing, avoiding cross-contamination or dilution of the residual liquid in the tubing for subsequent processing. This significantly improves the purification efficiency and processing accuracy of the protein solution, and enhances the stability and reliability of the entire protein solution processing device.

[0110] In some of the embodiments described above in this application, a sample storage unit is proposed for storing and processing protein solutions. However, during the transportation and processing of protein solutions, the sample storage unit may be connected to the external environment, which can easily lead to contamination of the protein solution by the external environment or changes in concentration due to evaporation, thereby affecting the accuracy and stability of protein solution processing.

[0111] In this regard, this application further proposes that the first sampling unit and / or the second sampling unit are provided with a sealing device.

[0112] like Figure 6 As shown, specifically, the sealing device aims to effectively isolate the protein solution inside the sample storage unit from the external environment. This sealing device can be implemented in various forms. For example, it can be a static seal achieved through a precision-machined cap threaded into the sample storage unit body, supplemented by O-rings or gaskets to ensure no leakage in a static state; it can also be a sealing cap using magnetic adsorption or snap-fit ​​connections to ensure quick opening and reliable closing during operation while providing sufficient sealing performance; or, in some applications with extremely high sealing requirements, permanent seals can be achieved through heat fusion or adhesive bonding to prevent any form of leakage or intrusion of external substances to the greatest extent possible.

[0113] In this regard, this application further proposes that the protein liquid processing device also includes an atmospheric pressure port, which is equipped with an air filter.

[0114] At the same time, such as Figure 7As shown, the air filtration device with an atmospheric pressure inlet functions primarily to maintain internal pressure balance while ensuring that the air entering the device is clean and uncontaminated. This air filtration device can utilize microporous membranes with specific pore sizes, such as those made of polytetrafluoroethylene (PTFE), polyethersulfone (PES), or polyvinylidene fluoride (PVDF), typically designed with pore sizes of 0.22 micrometers or 0.45 micrometers, effectively blocking airborne bacteria, viruses, particulate matter, and other pollutants. Alternatively, higher-level filtration media such as high-efficiency particulate air (HEPA) or ultra-high-efficiency particulate air (ULPA) filters can be used to meet applications with extremely high cleanliness requirements. In some cases, activated carbon filters can be combined to adsorb volatile organic compounds or harmful gases from the air, further enhancing air purity.

[0115] The above technical solution provides a highly controlled and clean environment for the storage and processing of protein solutions within the protein solution processing device. By installing sealing devices on the first and / or second sample units, direct contact between the protein solution and the external environment can be effectively prevented, thus avoiding concentration changes due to evaporation during processing and contamination caused by external impurities (such as dust and microorganisms). This is crucial for maintaining the original state of the protein solution and ensuring its purity and concentration stability, especially during long-term sample processing or storage, significantly improving the accuracy and reliability of the processing results.

[0116] Furthermore, by incorporating an air filtration device at the atmospheric pressure inlet, this application ensures that the air entering the device is rigorously filtered while allowing necessary pressure equalization exchange between the internal and external environments. This effectively prevents airborne particulate matter, microorganisms, and other contaminants from entering the protein solution processing system, thereby avoiding secondary contamination introduced during the pressure equalization process. This synergistic design allows the entire protein solution processing device to operate in a closed, clean, and pressure-stable environment, significantly reducing the risk of contamination or alteration of the protein solution's properties during transport, sample placement, and membrane filtration. Therefore, this application significantly improves the accuracy and stability of protein solution processing, providing a more reliable technical guarantee for the precise separation and purification of proteins in biomedical research and clinical diagnosis.

[0117] In some of the solutions described above in this application, an overall architecture for a protein liquid processing device is proposed. However, in the actual fluid drive and control process, how to achieve precise switching of protein liquid flow direction and pressure control through simplified and efficient component configuration, so as to avoid protein aggregation, precipitation and biochemical reaction interference caused by the complex pump and valve structure mentioned in the background art, remains a key problem that needs to be solved.

[0118] In response, this application proposes a protein liquid processing device, wherein the driving unit comprises a one-way pump, a first three-way valve, a second three-way valve, a third three-way valve, and a three-way interface.

[0119] Specifically, the drive unit is the core component of the protein liquid processing device, responsible for providing fluid power and controlling the fluid flow direction. Its main function is to generate pressure or flow rate to propel the protein liquid through the pipeline and switch between different paths according to processing requirements. Besides the unidirectional pump and three-way valve combination mentioned in this solution, the drive unit can also be a peristaltic pump, which regulates fluid flow and pressure by precisely controlling the pump's speed; alternatively, the drive unit can be a syringe pump, which provides stable fluid delivery through piston displacement. A unidirectional pump is a pump that can only deliver fluid in one direction. Its function is to provide stable, directional fluid power for the entire protein liquid processing system, ensuring that the protein liquid flows in a preset direction and avoiding backflow and unnecessary shear forces. For example, this unidirectional pump can be a diaphragm pump, which generates a pressure difference through the reciprocating motion of the diaphragm, driving the fluid to flow in one direction, and the fluid does not directly contact the pump's mechanical parts, thereby reducing contamination and shear; alternatively, a piston pump can be used, which achieves fluid intake and discharge through the linear reciprocating motion of the piston, providing higher pressure output. The first, second, and third three-way valves are all valves with three fluid ports, capable of switching the flow direction or mixing fluids according to control signals. In this solution, these three-way valves work together to precisely control the switching of protein solutions between different pipelines, achieving fluid diversion, merging, or path selection. For example, these three-way valves can be solenoid valves, controlling the movement of the valve core by energizing and de-energizing an electromagnetic coil, thereby changing the connectivity of the fluid channel, offering fast response and easy automation control; alternatively, they can be pneumatic valves, using compressed air to drive the actuator to control the valve's opening, closing, and flow direction, suitable for applications requiring high torque or explosion-proof features. A three-way connector is a pipeline connector with three connection ports, used to merge or divert three pipelines. In this solution, the three-way connector acts as a connection hub, effectively integrating the output of the unidirectional pump with multiple three-way valves, ensuring that the driving pressure is smoothly and evenly distributed to each processing unit. For example, the tee can be a Y-type connector, with its three ports arranged in a Y-shape, providing a smooth fluid transition and reducing turbulence; or it can be a T-type connector, with its three ports arranged in a T-shape, which is compact and easy to install.

[0120] like Figure 8As shown, through the above technical solution, this application utilizes a unidirectional pump as a stable power source, combined with a first three-way valve, a second three-way valve, a third three-way valve, and a three-way interface, to construct a modular drive control system. This configuration effectively simplifies the complexity of the fluid circuit and reduces dead zones in fluid contact, thereby minimizing the negative impact on the bioactivity of the protein solution while ensuring fluid transport efficiency. The use of a unidirectional pump avoids repeated retention and shearing of the fluid inside the pump body, significantly reducing the risk of protein aggregation and precipitation caused by mechanical stress. Simultaneously, the logical switching function of the three-way valve allows the device to flexibly guide the flow direction and distribute pressure between the first and second pipelines according to processing requirements, achieving precise control of the protein solution processing process. More importantly, the structural design of this drive control system supports simultaneous extrusion in two directions, greatly improving operational flexibility and processing efficiency, and effectively solving the problems of complex traditional pump and valve structures, easy protein damage, and inaccurate flow direction control.

[0121] In some of the embodiments described above in this application, a drive unit is proposed to realize the transport and processing of protein liquid. However, in practical applications, how to achieve precise switching of fluid flow direction and pressure control through a simple mechanical structure in order to avoid shear damage or aggregation effect on protein liquid caused by pump and valve structure remains a technical challenge that needs to be solved.

[0122] In response, this application further proposes a protein liquid processing device, wherein the drive unit specifically comprises a one-way pump, a first three-way valve, a second three-way valve, a third three-way valve, and a three-way interface. Specifically, the output end of the one-way pump is connected to the common end of the first three-way valve, the normally open end of the first three-way valve is connected to the first end of the three-way interface, the second and third ends of the three-way interface are respectively connected to the normally open ends of the second and third three-way valves, and the common ends of the second and third three-way valves are the first and second ports of the drive unit, respectively.

[0123] As the power source of the entire drive system, the unidirectional pump is responsible for providing stable fluid pressure or flow rate. Its working principle is typically based on mechanical motion, such as piston, diaphragm, or peristalsis, pushing fluid from the inlet to the outlet, ensuring fluid flow in a preset direction. For example, a peristaltic pump can be used, pushing fluid by squeezing a hose, or a diaphragm pump can be used, generating pressure through the reciprocating motion of the diaphragm. A three-way valve is a control element with three fluid ports, capable of switching fluid pathways according to control signals. In this embodiment, the three-way valve is used to precisely control the splitting and merging of fluids, thereby achieving flexible switching of flow direction. For example, an electromagnetic three-way valve can be used, controlling the opening and closing of the valve core by the on / off state of an electromagnetic coil, or a pneumatic three-way valve can be used, driving the valve action through a pneumatic pressure signal. A three-way connector is a passive fluid connection used to split a single fluid stream into two or merge two fluid streams into one. Its structure is simple, typically Y-shaped or T-shaped, ensuring smooth distribution of fluid between different paths. For example, an integrally molded Y-shaped connector or a modular T-shaped connector can be used.

[0124] Through the above technical solution, this application constructs a sophisticated flow path control system consisting of a unidirectional pump, multiple three-way valves, and a three-way interface. The system uses the unidirectional pump to provide stable power, and the pump's output pressure is introduced into the three-way interface for flow distribution via the first three-way valve. The three-way interface symmetrically distributes the pressurized fluid to the normally open ends of the second and third three-way valves, while the common ends of these two three-way valves serve as the first and second ports of the drive unit, respectively. This design allows the drive unit to flexibly control the pressure difference between the first and second pipelines, thereby achieving precise transport of the protein solution in the membrane filtration unit. For example, by simultaneously opening the second and third three-way valves, the first and second pipelines can be pressurized simultaneously, creating a bidirectional co-drive effect; or by selectively opening one of the valves, unidirectional drive can be achieved. This valve logic combination not only simplifies the complexity of the drive system and avoids the protein aggregation and precipitation problems that may be caused by traditional reciprocating pumps, but also effectively reduces the mechanical shear force on the protein solution through precise control of fluid flow direction and pressure, thereby ensuring the accuracy and effect of protein solution treatment and providing a reliable hardware foundation for stable protein solution treatment.

[0125] In some of the solutions described above in this application, a protein liquid processing device consisting of a drive unit, a sample collection unit, and a membrane filtration unit is proposed to realize the transport and processing of protein liquid. However, in actual operation, due to the tendency of protein liquid to aggregate, precipitate, or be affected by the structure of pumps and valves, if the drive method is singular or lacks flexible switching control of the fluid path, it is difficult to achieve efficient and stable fluid drive in complex pipeline systems, resulting in limited processing accuracy and purification effect.

[0126] In response, this application further proposes a protein solution processing method, which includes a bidirectional co-drive step. In the bidirectional co-drive step, the three-way interface simultaneously connects to the common end of the second three-way valve and the third three-way valve, and / or, the three-way interface connects only to one of the common ends of the second three-way valve and the third three-way valve.

[0127] The bidirectional co-drive step refers to the process where, during protein solution treatment, a driving unit applies driving force to the fluid, causing it to be transported or squeezed simultaneously in two directions within the pipeline system. This step aims to further squeeze the remaining gel-like substance in both directions after the protein solution has been initially concentrated and formed a gel, thereby further removing residual water from the gel. Specifically, the driving unit can be controlled to periodically switch driving directions within a specific time period, for example, driving forward for a period and then driving in the opposite direction for a period, creating a reciprocating motion. This allows for the initial concentration of the protein solution and the formation of a gel. Alternatively, both ports of the driving unit can be activated simultaneously, causing the fluid to be driven and squeezed simultaneously in different branches of the pipeline, further squeezing out the protein solution. Some water in the gel-like substance is then further removed through a filter membrane, completing the final enrichment and purification.

[0128] The simultaneous connection of the three-way interface to the common ends of the second and third three-way valves means that, under the control of the drive unit, both the common ends of the second and third three-way valves are simultaneously connected to the driving force source. According to the structure of the protein liquid processing device described above, the common ends of the second and third three-way valves correspond to the first and second ports of the drive unit, respectively. Therefore, this indicates that the first and second ports of the drive unit are activated simultaneously. This operation allows the driving force to act simultaneously on two different paths or directions in the piping system, thereby achieving synchronous pushing or squeezing of the fluid within the piping. This is crucial for efficient liquid separation and effective substance concentration at the membrane filtration unit. For example, through the control logic within the drive unit, when the drive unit is a gas-driven device, gas pressure can be applied simultaneously to the piping connected to the common ends of the second and third three-way valves; or, if the drive unit contains multiple independent drive sources or independently controllable channels, these channels can be activated simultaneously, establishing connections with the common ends of the second and third three-way valves, respectively.

[0129] In other unidirectional drive steps, the drive unit connects only one of the common ends of the second and third three-way valves. This means that under the control of the drive unit, only one of the common ends of the second and third three-way valves is connected to the drive source. This implies that only one of the first and second ports of the drive unit is activated. This operation provides flexibility in fluid path selection, allowing for directional transport or segmented processing of the protein solution. This helps guide the fluid to the desired path at specific stages, avoiding unnecessary circulation or stagnation in non-target areas, thereby improving processing efficiency and reducing protein loss. For example, through the control system of the drive unit, when the drive unit is a gas-driven device, gas pressure can be applied only to the pipeline connected to the common end of the second three-way valve, while keeping the pipeline connected to the common end of the third three-way valve in a non-driven state, and vice versa; or, if the drive unit contains independently switchable valves or channels, the state of these valves or channels can be switched to connect only one of them to the drive source, thereby achieving drive of a single-directional path.

[0130] By introducing a bidirectional co-drive step and combining it with the flexible connection control of the common ends of the second and third three-way valves by the drive unit, the transport efficiency and processing effect of the protein solution in the pipeline system are significantly improved. When the drive unit simultaneously connects the common ends of the second and third three-way valves, synchronous pushing of the fluid in the pipeline is achieved. This parallel drive method helps to balance the pressure distribution in the pipeline, reduce local retention of the protein solution or excessive shear force caused by pressure difference, thereby protecting protein activity and improving the uniformity of processing. More importantly, this bidirectional squeezing function is similar to the spin-drying process of a washing machine, which can effectively squeeze the liquid in the membrane filtration unit out of the filter membrane. After multiple forward and reverse transport and filtration, most of the liquid in the protein solution flows away through the filter membrane. The bidirectional squeezing of the bidirectional co-drive step for a period of time forces the water to be squeezed out, greatly increasing the content of effective substances and solving the problem of low content of effective substances in traditional methods, thus making the subsequent possible freeze-drying process more effective. When the drive unit connects only to one of the common ends of the second and third three-way valves, it provides flexibility in path selection, enabling directional transport or segmented processing of the protein solution. This selective drive mechanism allows the device to flexibly switch flow directions according to processing requirements, further reducing the negative impact of protein solution contact with the device's internal structure and minimizing the risk of protein aggregation and precipitation. In summary, through logical control of valve connection status in the bidirectional co-drive step, precise spatial distribution of driving force and dynamic regulation of fluid paths are achieved, optimizing the fluid flow state in the pipeline, reducing ineffective fluid retention in complex structures, and significantly improving the stability and purification efficiency of protein solution processing, especially demonstrating excellent performance in protein concentration and extraction of effective substances.

[0131] In some of the embodiments described above in this application, a bidirectional co-drive method is proposed to achieve protein liquid processing. However, in the actual protein liquid processing process, due to the lack of a targeted control strategy for the operating parameters of the drive unit, the driving force output may be unstable or the processing efficiency may be low, making it difficult to ensure the accuracy of protein liquid transport and processing effect under complex working conditions.

[0132] To address this, this application further proposes that in the bidirectional co-drive step, the drive unit operates continuously at maximum power for a specific duration. Here, "maximum power" refers to the highest working capacity that the drive unit can output within its design limits. This ensures that during protein solution processing, the drive unit can provide sufficient power to overcome pipeline resistance, fluid viscosity, and potential obstacles from the membrane filtration unit, thereby guaranteeing effective protein solution transport. One implementation method is to achieve maximum power output by adjusting the input voltage or current of the drive unit to its rated maximum value. Another implementation method, for gas-driven devices, is that maximum power can be expressed as maximum output pressure or maximum flow rate, achieved by controlling the gas source pressure or flow regulating valve. Yet another implementation method is to directly set the operating mode of the drive unit to maximum power output mode through the control module within the drive unit.

[0133] "Continuous operation" refers to the drive unit maintaining its maximum power output without interruption for a set period of time. This continuity ensures that the protein solution receives a stable and strong driving force throughout the entire processing cycle, avoiding flow rate instability or uneven processing caused by power fluctuations or intermittent driving. One way to achieve this is through real-time monitoring and feedback adjustment of the drive unit's operating status by a controller, ensuring that it maintains maximum power output throughout the specific time period. Another approach is to use open-loop control, where once the maximum power mode is activated, it is preset not to adjust power for a specific period of time.

[0134] "Specific duration" refers to a precise time period that is pre-set or dynamically calculated for the maximum power operation of the drive unit. This time period is designed to achieve quantitative control of the protein solution processing, ensuring sufficiency and efficiency. One approach is to determine this specific duration through experimental testing, experience accumulation, or theoretical calculations, for example, by pre-setting parameters such as the volume, viscosity, tubing geometry, and characteristics of the membrane filtration unit. Another approach is to dynamically adjust this specific duration based on real-time monitoring of processing progress or liquid level changes through the control system. Yet another approach is to precisely control the operating time of the drive unit using a timer module integrated into the control system.

[0135] Through the above technical solution, in the bidirectional co-drive step, the drive unit operates at maximum power continuously for a specific duration, effectively solving the problems of unstable drive force output and low processing efficiency. Specifically, the drive unit operates at maximum power, ensuring a sufficient and stable drive force throughout the protein solution processing. This effectively overcomes the resistance within the first and second pipelines and the membrane filtration unit, guaranteeing that the protein solution can pass through the membrane filtration unit efficiently and quickly. Simultaneously, by setting a specific operating time, quantitative control of the processing is achieved, avoiding energy waste or unnecessary pressure accumulation due to excessively long drive times, and also preventing insufficient protein solution processing due to excessively short drive times. This control method, combining the output capacity of the drive unit with the time dimension, ensures that the stress state of the protein solution in the entire processing device remains within a controllable range, thereby significantly improving the reliability and consistency of protein solution processing. Especially during bidirectional co-drive operations, it enables more precise control of the protein solution's transport path and processing effect.

[0136] The following example will provide a more detailed explanation of the above technical solution: In a biological laboratory, small liquid samples containing specific proteins need to be filtered through membranes to remove impurities and obtain purified proteins. This process requires minimizing protein aggregation, precipitation, and biochemical reactions that may occur due to contact with the internal structure of the equipment, thereby ensuring the precision of separation and purification.

[0137] To address this, the laboratory employed a protein solution processing device. The core of this device is a drive unit comprising a first port and a second port. This drive unit is a gas-driven device consisting of a one-way pump, a first three-way valve, a second three-way valve, a third three-way valve, and a three-way connector. The output of the one-way pump is connected to the common terminal of the first three-way valve, and the normally open terminal of the first three-way valve is connected to the first terminal of the three-way connector. The second and third terminals of the three-way connector are connected to the normally open terminals of the second and third three-way valves, respectively. The common terminals of the second and third three-way valves are the first and second ports of the drive unit, respectively. This design ensures that the protein solution does not flow through the first and second ports of the drive unit, thus avoiding direct contact between the protein and the complex internal structure of the pump and valves, effectively solving the problems of protein aggregation and precipitation that may occur with traditional pumps and valves.

[0138] The device also includes a first nanosample unit, the volume of which is designed to be larger than the sum of the volumes of the first tubing, the second tubing, and the membrane filtration unit to ensure sufficient sample processing capacity. The first nanosample unit includes a third port and a fourth port, wherein the third port is connected to the second port of the drive unit. The first nanosample unit is also equipped with a sealing device to prevent external contamination.

[0139] A membrane filtration unit is used to filter protein liquids and includes a fifth port and a sixth port.

[0140] To connect these components, the device is equipped with a first conduit and a second conduit. The first conduit is made of an opaque and bio-inert material, such as polyetheretherketone (PEEK), which helps protect light-sensitive proteins and prevents protein adsorption or reaction with the conduit wall. The wall thickness of the first conduit is 8%-30% of its outer diameter, the inner diameter is greater than or equal to 0.5 mm, and the outer diameter is less than or equal to 5 mm. These dimensions are suitable for efficient transport of small volumes of liquid. The fourth port of the first nanosample unit is connected to one end of the first conduit, and the other end of the first conduit is connected to the fifth port of the membrane filtration unit.

[0141] The sixth port of the membrane filtration unit connects to one end of the second conduit. The second conduit is also made of an opaque and bio-inert material, with similar wall thickness, inner diameter, and outer diameter as the first conduit. The other end of the second conduit connects to the seventh port of a second nanosample unit. The volume of the second nanosample unit is also larger than the sum of the volumes of the first conduit, the second conduit, and the membrane filtration unit, and it is equipped with a sealing device. The eighth port of the second nanosample unit connects to the first port of the drive unit. The entire device also includes an atmospheric pressure port equipped with an air filter to ensure that the gas entering the system is clean and uncontaminated.

[0142] To precisely control liquid transport, a first liquid level detection unit is installed on the outer wall of the first conduit, and a second liquid level detection unit is installed on the outer wall of the second conduit. Both liquid level detection units are non-contact detection units; specifically, they are acoustic field liquid level detection units. The acoustic field liquid level detection unit has a response time of less than 10 ms for air detection and less than 1 s for liquid detection, with an ultrasonic intensity (Ispta) of less than 100 mW / cm². This non-contact detection method avoids contamination or interference to proteins that may be introduced by traditional contact sensors, while the low ultrasonic intensity ensures that the protein structure is not damaged. The distance from the detection point of the first liquid level detection unit to the end of the first conduit connecting to the first nanosample unit is greater than or equal to three times the distance from the detection point to the end of the first conduit connecting to the membrane filtration unit. Similarly, the distance from the detection point of the second liquid level detection unit to the end of the second conduit connecting to the second nanosample unit is greater than or equal to three times the distance from the detection point to the end of the second conduit connecting to the membrane filtration unit. This layout of detection points helps to accurately monitor the liquid level in critical areas, preventing air bubbles from entering or liquid from overflowing.

[0143] In practice, the user injects the liquid protein sample to be processed into the first nanosample unit. Subsequently, the drive unit is activated, for example, by performing a bidirectional co-drive step, simultaneously connecting the common end of the second and third three-way valves, or connecting only one of them. The unidirectional pump of the drive unit generates clean compressed air, which is applied to the liquid surface within the first nanosample unit through the second port of the drive unit and the third port of the first nanosample unit. Because the liquid protein does not flow directly through the drive unit, contact with the complex internal structure of the pump is avoided, thus significantly reducing the risk of protein aggregation and precipitation.

[0144] Gas pressure propels the protein liquid from the fourth port of the first nano-sample unit into the first conduit. As the liquid flows through the first conduit, the first liquid level detection unit monitors the liquid level in real time using a non-contact method. Its rapid response capability allows the system to precisely control the fluid front, ensuring a smooth and continuous delivery of the liquid to the fifth port of the membrane filtration unit. In the membrane filtration unit, the protein liquid is filtered, and impurities are retained.

[0145] The filtered purified protein liquid flows out from the sixth port of the membrane filtration unit and into the second tubing. The second liquid level detection unit also monitors the liquid level in the second tubing in a non-contact manner. The liquid then flows to the seventh port of the second nano-sample unit. If necessary, the purified protein liquid can be collected in the second nano-sample unit, or, by applying gas pressure through the first port of the drive unit and the eighth port of the second nano-sample unit, the liquid can be recirculated or transported to other processing stages. In the bidirectional co-drive step, the drive unit can operate at maximum power continuously for a specific duration to ensure the integrity of liquid transport or filtration.

[0146] Through the aforementioned apparatus and method, this protein liquid processing device achieves gentle and efficient processing of protein liquid samples. The design of non-contact liquid level detection, bio-inert tubing, and gas-driven unit collectively solves the technical problems of protein susceptibility to damage, contamination, and aggregation / precipitation in traditional methods, thereby improving the accuracy and effectiveness of protein separation and purification.

[0147] The above are merely embodiments of this application and are not intended to limit the scope of protection of this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the scope of protection of this application.

Claims

1. A protein liquid processing device, characterized in that, It includes a first pipeline, a second pipeline, a first sampling unit, a first liquid level detection unit, a second liquid level detection unit, a drive unit, and a membrane filtration unit. The drive unit includes a first port and a second port. The first sampling unit includes a third port and a fourth port. The membrane filtration unit includes a fifth port and a sixth port. The second port of the driving unit is connected to the third port of the first sampling unit. The fourth port of the first sampling unit is connected to one end of the first pipeline. The other end of the first conduit is connected to the fifth port of the membrane filtration unit. The sixth port of the membrane filtration unit is connected to one end of the second pipeline. The other end of the second conduit is connected to the first port of the drive unit. The first liquid level detection unit is installed on the outer wall of the first pipeline. The second liquid level detection unit is installed on the outer wall of the second pipeline. Both the first liquid level detection unit and the second liquid level detection unit are non-contact detection units.

2. A protein liquid processing apparatus as described in claim 1, characterized in that, Both the first liquid level detection unit and the second liquid level detection unit are acoustic field liquid level detection units. in, The response time of the acoustic field liquid level detection unit during air detection is less than 10ms. And / or, the response time of the acoustic field liquid level detection unit during liquid detection is less than 1 second.

3. A protein liquid processing apparatus as described in claim 2, characterized in that, The ultrasonic intensity Ispta of the acoustic field liquid level detection unit is < 100 mW / cm. 2 , And / or, the response time of the acoustic field liquid level detection unit during liquid detection is greater than or equal to 10 times the response time of the acoustic field liquid level detection unit during air detection.

4. A protein liquid processing apparatus as described in claim 1, characterized in that, Both the first and second conduits are made of opaque materials. Both the first and second pipelines are made of bio-inert materials.

5. A protein liquid processing apparatus as described in claim 1, characterized in that, The protein solution processing device also includes a second nano-sample unit. The second sampling unit includes a seventh port and an eighth port. The other end of the second conduit is connected to the seventh port of the second sampling unit. The eighth port of the second sampling unit is connected to the first port of the driving unit.

6. A protein liquid processing apparatus as described in claim 5, characterized in that, The distance from the detection point of the first liquid level detection unit to the end of the first pipeline connected to the first sampling unit is the pipeline length. The distance from the detection point to one end of the first pipeline connecting to the membrane filtration unit is greater than or equal to three times the length of the pipeline. And / or, The distance from the detection point of the second liquid level detection unit to the end of the second pipeline connected to the second sampling unit is the length of the pipeline. The distance from the detection point to the end of the second pipeline connected to the membrane filtration unit is greater than or equal to three times the length of the pipeline.

7. A protein liquid processing apparatus as described in claim 1, characterized in that, The driving unit is a gas-driven device. And / or, the protein solution does not flow through the first port and the second port.

8. A protein liquid processing apparatus as described in claim 5, characterized in that, The first sampling unit and / or the second sampling unit are equipped with a sealing device. And / or, the protein liquid processing device further includes an atmospheric pressure port, which is equipped with an air filter.

9. A protein liquid processing apparatus as described in claim 1, characterized in that, The drive unit includes a one-way pump, a first three-way valve, a second three-way valve, a third three-way valve, and a three-way interface. The output end of the unidirectional pump is connected to the common end of the first three-way valve. The normally open end of the first three-way valve is connected to the first end of the three-way interface. The second and third ends of the three-way connector are respectively connected to the normally open ends of the second three-way valve and the third three-way valve. The common terminals of the second three-way valve and the third three-way valve are respectively the first port and the second port of the drive unit.

10. A protein liquid treatment method using the protein liquid treatment apparatus as described in claim 9, characterized in that, Includes a bidirectional co-drive step, In the bidirectional co-drive step, the three-way interface is simultaneously connected to the common end of the second three-way valve and the third three-way valve.

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