Blood product virus inactivation system based on synergistic effect of nano-catalysis photochemical inactivation and low-temperature plasma
Through the blood product virus inactivation system that synergizes nanocatalytic photochemistry and low-temperature plasma, the problem of limited and uneven virus inactivation effects in the prior art is solved, and efficient and uniform virus inactivation is achieved, while maintaining the biological activity and safety of blood products.
Patent Information
- Application Number
- CN202510482822.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-17
- Publication Date
- 2025-07-29
AI Technical Summary
The existing virus inactivation technology of blood products has problems such as limited inactivation effect, limited effect on enveloped viruses, low inactivation rate of ultraviolet-resistant viruses, chemical treatment damages blood components, and uneven inactivation.
Nanocatalytic photochemical inactivation and low-temperature plasma synergistically, TiO2 and g-C3N4 nanomaterials are used to generate high-reactive oxygen free radicals, combined with low-temperature plasma to release active particles, ensure uniform inactivation through microfluidic mixing and intelligent feedback modules, and parameters are optimized using AI adaptive regulation algorithm.
Efficient and uniform virus inactivation is achieved, the biological activity of blood products is maintained, the inactivation rate is improved to 99.99%, chemical residues and temperature damage are avoided, and biosafety and environmental protection requirements are met.
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Figure CN120381542A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to, but is not limited to, the field of medical technology, and particularly relates to a blood product virus inactivation system based on the synergistic effect of nano-catalytic photochemical inactivation and low-temperature plasma. Background Art
[0002] Currently, the virus inactivation of blood products mainly relies on ultraviolet irradiation (UV) and chemical treatment (such as the solvent-detergent method) (Note: Currently, the virus inactivation of blood products is mainly the pasteurization inactivation process). This method uses ultraviolet radiation to destroy the nucleic acid of the virus and combines with chemical treatment agents to destroy the lipid envelope of the virus, thereby inactivating the virus and improving the safety of blood products.
[0003] Although the combined inactivation technology of ultraviolet and chemical treatment can effectively kill viruses to a certain extent, there are still the following problems:
[0004] 1. Limited virus inactivation effect:
[0005] The existing ultraviolet inactivation method mainly acts on naked viruses and has limited effect on enveloped viruses (such as hepatitis B virus HBV and human immunodeficiency virus HIV).
[0006] Some ultraviolet-resistant viruses (such as certain enteroviruses) have high resistance to ultraviolet irradiation and low inactivation rate.
[0007] 2. Damage to blood product components:
[0008] Traditional chemical treatment methods may destroy active proteins such as coagulation factors, immunoglobulins, and albumin in the blood, affecting the function of blood products.
[0009] Strong ultraviolet irradiation is likely to cause plasma protein denaturation and reduce the quality of blood products.
[0010] 3. Uneven inactivation:
[0011] The penetration power of ultraviolet rays is limited, which easily leads to uneven virus inactivation effects between the inner and outer layers of blood products, increasing the risk of residual viruses. Summary of the Invention
[0012] Aiming at the problems existing in the prior art, the present invention provides a blood product virus inactivation system based on the synergistic effect of nano-catalytic photochemical inactivation and low-temperature plasma.
[0013] The present invention is realized as follows. A blood product virus inactivation system based on the synergistic effect of nano-catalytic photochemical inactivation and low-temperature plasma, the system includes:
[0014] The nano-photocatalytic inactivation module uses titanium dioxide (TiO2) and graphitic carbon nitride (g-C3N4) nanomaterials as photocatalysts. Under the irradiation of LEDs with specific wavelengths of 365 nm - 450 nm, highly reactive oxygen species (ROS) are generated to destroy the nucleic acid and protein structures of viruses.
[0015] The low-temperature plasma inactivation module uses a low-temperature plasma generator to generate a plasma cloud above the blood products and release active particles such as electrons, ions, and hydroxyl radicals (OH·) to destroy the viral membrane proteins and improve the inactivation efficiency.
[0016] The dynamic fluid stirring module uses microfluidic mixing technology to ensure that the blood products are uniformly exposed to the photocatalytic and plasma inactivation effects, ensuring the uniformity of virus inactivation.
[0017] The sensing monitoring and intelligent feedback module uses spectral sensors and biochemical sensors to continuously monitor the residual amount of viral nucleic acid and protein activity in the blood, and optimizes the inactivation parameters such as light intensity, plasma power, and time through an AI adaptive control algorithm.
[0018] Furthermore, the main reaction equations of the nano-photocatalytic inactivation module are as follows:
[0019] Electron transition of the photocatalyst:
[0020] TiO2 + hv(λ = 365 nm - 450 nm) → e - + h +
[0021] where e - is the photo-generated electron, and h + is the hole;
[0022] Generation of reactive oxygen species (ROS):
[0023] O2 + e - → O2 -
[0024] H2O + h + → OH· + H +
[0025] Superoxide anion (O2 - ·) and hydroxyl radical (OH·) have extremely strong oxidation capabilities and can degrade the viral protein coat and RNA / DNA.
[0026] Virus inactivation process:
[0027] RNA / DNA + OH· → Degradation products
[0028] Viral membrane protein + O2 - → Structural damage
[0029] These highly reactive oxygen species can break the nucleic acid chain of the virus, rendering it unable to replicate. At the same time, they degrade the viral envelope proteins, ultimately achieving the effect of virus inactivation.
[0030] Furthermore, the key role of the plasma in the low-temperature plasma inactivation module is as follows:
[0031] (1) Generation of plasma active particles:
[0032] N2 + e - →N2 * + e -
[0033] O2 + e - →O2 - + O·
[0034] Among them, N2 * represents the excited state nitrogen molecule, and O· represents the single atomic oxygen free radical;
[0035] (2) Virus inactivation mechanism:
[0036] Protein denaturation: OH· and O· will damage the membrane proteins of the virus, making the virus unable to recognize host cells and lose its infectivity;
[0037] RNA / DNA degradation: The high-energy electrons and superoxide anions released by the plasma will directly attack the viral nucleic acid, resulting in the breakage of the gene chain and making the virus lose its reproductive ability.
[0038] (3) Gentle treatment:
[0039] The temperature of the low-temperature plasma does not exceed 40 °C, which will not affect the protein activity in the blood product and ensure safety.
[0040] Furthermore, the working mechanism of the dynamic fluid stirring module is as follows:
[0041] (1) Microfluidic mixing
[0042] The blood product is made to flow in the inactivation chamber through a microfluidic pump and come into full contact with the catalyst.
[0043] Using the principle of laminar flow mixing, the fluid flow path is optimized to ensure the uniformity of virus inactivation.
[0044] (2) Electromagnetic stirring
[0045] An electromagnetic stirring device is used to generate a rotational flow inside the blood product, making the photocatalysis and plasma effects more uniform and improving the inactivation effect.
[0046] Furthermore, the working mechanism of the sensing monitoring and intelligent feedback module is as follows:
[0047] (1) Sensor monitoring
[0048] Spectral sensor: Real-time detection of virus nucleic acid content, fluorescence detection;
[0049] Biochemical sensor: Detection of blood component changes to ensure that protein activity is not damaged;
[0050] (2) Intelligent AI regulation
[0051] Adaptive AI algorithm is adopted to analyze the data during the inactivation process and dynamically adjust the light intensity, plasma power and inactivation time;
[0052] Through the PID closed-loop control system, ensure that the inactivation error is controlled within ±1%.
[0053] Another object of the present invention is to provide a method for inactivating viruses in blood products based on the synergistic effect of the above-mentioned nano-catalytic photochemical inactivation + low-temperature plasma. This method specifically includes:
[0054] S1: Pretreatment of blood products
[0055] Adopt gentle centrifugation separation technology to fully mix blood products such as plasma, red blood cells, and platelets with virus contaminants to ensure uniform distribution; adjust the blood pH value to 7.2 - 7.4 to maintain the best virus inactivation effect.
[0056] S2: Nano-photocatalytic virus inactivation
[0057] Function of photocatalyst:
[0058] Add nano-photocatalytic material (TiO2 / g-C3N4) to the blood product; irradiate with an LED light source (365 - 450 nm) to activate the photocatalyst to generate hydroxyl radicals (OH·), superoxide anions (O2 - ) and singlet oxygen ( 1 O2);
[0059] These reactive oxygen free radicals can react with virus proteins and nucleic acids to destroy the virus structure.
[0060] Dynamic fluid stirring:
[0061] Adopt microfluidic stirring technology to make the photocatalyst evenly distributed in the blood product and improve the virus inactivation efficiency;
[0062] S3: Synergistic inactivation with low-temperature plasma
[0063] Plasma generation:
[0064] A low-temperature plasma generator is used to form a plasma cloud above the blood product;
[0065] The low-temperature plasma releases high-energy electrons, ions, and OH· free radicals to further damage virus proteins and nucleic acids;
[0066] Dynamic feedback regulation:
[0067] The residual virus nucleic acid is monitored by a sensor, and the intensity and action time of the plasma are intelligently controlled to ensure that the inactivation effect reaches more than 99.99%;
[0068] S4: Post-treatment and quality inspection
[0069] Biosensors and PCR technology are used to detect the residual virus situation to ensure that the inactivation meets medical safety standards such as FDA and WHO standards;
[0070] The activity of blood proteins is detected by ELISA to ensure that the inactivation process does not affect the quality of blood products.
[0071] Combined with the above technical solutions and the solved technical problems, the advantages and positive effects of the technical solution to be protected by the present invention are as follows:
[0072] First, based on the synergistic effect of nano-catalytic photochemical inactivation and low-temperature plasma, the present invention realizes efficient virus inactivation of blood products. This technology uses reactive oxygen species (ROS) generated by photocatalytic reactions and plasma chemical reactions induced by low-temperature plasma (LTP) to damage virus envelopes, nucleic acids, and proteins, thereby inactivating various pathogens (including HBV, HIV, HCV, etc.). Compared with traditional solvent-detergent (SD) chemical inactivation methods, this method does not rely on exogenous chemical reagents, avoids the influence of chemical residues on blood components, and maximally maintains blood activity while maintaining a high inactivation rate.
[0073] This technology uses nano-TiO2 and ZnO photocatalysts to generate highly efficient hydroxyl radicals (·OH), superoxide anion radicals (O2 - ·), etc. with strong oxidizing properties under the excitation of ultraviolet light (UVA 365nm), causing irreversible damage to virus envelopes and nucleic acids. In addition, the low-temperature plasma module generates excited molecules (O, N2*), electrons, ultraviolet light, and electric fields through high-voltage glow discharge, synergistically with photocatalytic oxidation, to improve the virus inactivation efficiency. The operating temperature of the low-temperature plasma is ≤ 40°C, ensuring the stability of bioactive substances such as plasma proteins and coagulation factors and avoiding the problem of protein denaturation caused by temperature increase.
[0074] To improve the inactivation uniformity, this method adopts a microfluidic dynamic mixing + electromagnetic stirring system to ensure the uniform flow of blood samples in the photocatalytic and plasma inactivation zones, avoiding the uneven inactivation problem caused by the limited light penetration depth during traditional ultraviolet inactivation. The hydrodynamic optimization design ensures the normalization of the residence time of blood samples in the plasma reaction zone, making virus inactivation more thorough. In addition, the catalyst nanoparticles can be recycled through magnetic separation technology, avoiding the residue of the catalyst in the blood and ensuring biological safety.
[0075] This system is equipped with an AI intelligent monitoring and feedback control module to monitor the inactivation status of blood samples in real time, including the degradation of viral RNA / DNA, the change of plasma protein structure, and inactivation parameters (light intensity, plasma electric field intensity, flow rate, etc.). The AI adaptive algorithm automatically adjusts the inactivation parameters based on sensor data, ensuring the best inactivation effect while avoiding damage to blood activity. This intelligent control system reduces manual intervention, improves the production automation level, optimizes the inactivation efficiency, and at the same time ensures the standardized processing of blood products.
[0076] Compared with traditional virus inactivation technologies, this method has significant safety and environmental protection advantages. Chemical inactivation methods (such as the SD method) are prone to chemical residues, which may cause immune reactions or allergic reactions; heat inactivation methods (such as pasteurization) are likely to damage the biological active factors in the blood and affect their therapeutic effects. This invention adopts pure physical and photochemical methods, without chemical reagent residues and no toxic by-products, fully meeting the requirements of biosafety and environmental protection. Its application scope is wide, and it can be used in the blood products industry (such as plasma protein products, albumin, immunoglobulin products), clinical blood transfusion safety, control of viral blood contamination, and the biopharmaceutical industry, providing a new guarantee technology for the safety of blood products. Brief Description of the Drawings
[0077] Figure 1 It is the structural diagram of the blood product virus inactivation system based on the synergistic effect of nano-catalytic photochemical inactivation + low-temperature plasma provided by the embodiment of the present invention;
[0078] Figure 2 It is the working mechanism flow chart of the dynamic fluid stirring module provided by the embodiment of the present invention;
[0079] Figure 3 It is the flow chart of the blood product virus inactivation method based on the synergistic effect of nano-catalytic photochemical inactivation + low-temperature plasma provided by the embodiment of the present invention;
[0080] In the figure: 1. Nano-photocatalytic inactivation module; 2. Low-temperature plasma inactivation module; 3. Dynamic fluid stirring module; 4. Sensing monitoring and intelligent feedback module. Detailed Embodiments
[0081] To make the objectives, technical solutions and advantages of the present invention more clear and understandable, the present invention will be further described in detail below in conjunction with embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.
[0082] As Figure 1 shown, an embodiment of the present invention provides a blood product virus inactivation system based on the synergistic effect of nano-catalytic photochemical inactivation + low-temperature plasma. The system includes:
[0083] The nano-photocatalytic inactivation module 1 uses titanium dioxide (TiO2) and graphitic carbon nitride (g-C3N4) nano-materials as photocatalysts. Under the irradiation of a specific wavelength of 365 nm - 450 nm LED, highly reactive oxygen species (ROS) are generated to destroy the virus nucleic acid and protein structure.
[0084] The low-temperature plasma inactivation module 2 uses a low-temperature plasma generator to generate a plasma cloud above the blood product and release active particles such as electrons, ions, and hydroxyl radicals (OH·) to destroy the virus membrane protein and improve the inactivation efficiency.
[0085] The dynamic fluid stirring module 3 uses microfluidic mixing technology to enable the blood product to uniformly receive the photocatalytic and plasma inactivation effects, ensuring the uniformity of virus inactivation.
[0086] The sensing monitoring and intelligent feedback module 4 uses spectral sensors and biochemical sensors to real-time monitor the residual amount of virus nucleic acid and protein activity in the blood, and optimizes the inactivation parameters such as light intensity, plasma power, and time through an AI adaptive control algorithm.
[0087] 1. Nano-photocatalytic inactivation module (module 1)
[0088] This module is based on the synergistic photocatalytic effect of the nano-materials titanium dioxide (TiO2) and graphitic carbon nitride (g-C3N4) to achieve efficient inactivation of viruses in blood products. By introducing LED irradiation of a specific wavelength (365 nm - 450 nm), photo-generated electrons and holes are generated between TiO2 and g-C3N4 under light irradiation conditions, thereby exciting the generation of highly reactive oxygen species (Reactive Oxygen Species, ROS), including hydroxyl radicals (OH·), superoxide radicals (O2 - ·) and singlet oxygen ( 1 O2). These highly reactive oxygen species can rapidly undergo redox reactions with the nucleic acid and protein of the virus (such as envelope protein and capsid protein), resulting in their inactivation and structural damage. The optimal concentration of the photocatalyst is 0.1 - 0.5 mg / mL, and the light intensity is 30 - 80 mW / cm 2, the processing time is controlled within 20 - 60 minutes to ensure a balance between efficient inactivation and protection of the activity of biological products.
[0089] 2. Low-temperature plasma inactivation module (Module 2)
[0090] This module uses a low-temperature plasma generator to generate a plasma cloud on or above the surface of blood products, forming a complex active system composed of high-energy electrons, positive and negative ions, free radicals, and neutral active molecules. Under the action of low-temperature plasma, reactions such as ionization, excitation, dissociation, and recombination occur simultaneously, generating a large number of active particles (such as OH·, O2 - ·, H2O2, e - ), and these particles destroy the membrane proteins and nucleic acids of viruses through direct action and indirect chemical reactions. The optimal plasma parameters are: discharge power 50 - 150W, operating frequency 13.56MHz or 2.45GHz, and processing time 10 - 30 minutes. By controlling the generation area of plasma and the flow rate of blood products, a comprehensive inactivation treatment of blood products can be achieved.
[0091] 3. Dynamic fluid stirring module (Module 3)
[0092] To ensure the uniformity and efficiency of the photocatalysis and plasma effects, this module uses microfluidic mixing technology to construct a dynamic fluid stirring system. When blood products flow in the microfluidic channel, through the design of multi-stage serpentine micro-mixers and vortex generators, the laminar flow and turbulent flow of the fluid are alternated to improve the uniform mixing and mass transfer efficiency of substances. The optimal flow rate range is 0.1 - 0.5 mL / min to ensure that the active particles of photocatalysis and plasma can fully act on each component of blood products. Through multi-point detection and flow rate optimization algorithms, the uniformity and efficiency during the inactivation process are ensured, avoiding the risk of virus residue caused by local overexposure or incomplete treatment.
[0093] 4. Sensing monitoring and intelligent feedback module (Module 4)
[0094] This module integrates a spectroscopic sensor and a biochemical sensor system to monitor and feedback optimize the virus inactivation effect in blood products in real time. Spectroscopic sensors (such as UV-Vis spectrometers and fluorescence spectrometers) are used to detect the residual virus nucleic acid and the generation rate of oxidizing species; biochemical sensors (such as electrochemical sensors and surface plasmon resonance sensors) are used to detect the structural integrity and biological activity of proteins in blood products. By comparing the signal changes before and after the photocatalysis and plasma treatment, the real-time status of virus inactivation is obtained. Using AI adaptive control algorithms (such as deep reinforcement learning and particle swarm optimization algorithms), the light intensity, plasma power, and treatment time are automatically adjusted according to the detection results to optimize the inactivation efficiency and the quality of the finished product. The optimization frequency of the intelligent feedback system is set to once every 0.5 seconds to ensure real-time and accuracy.
[0095] 5. Synergistic mechanism and optimization strategy
[0096] In the present invention, the synergistic effect of nano-photocatalysis and low-temperature plasma shows a significant synergistic enhancement effect. The ROS generated during the photocatalysis process interacts with the active particles in the plasma cloud to form a higher concentration of oxidizing substances, thus significantly improving the efficiency of virus inactivation. Through the optimized design of the dynamic fluid stirring module, the uniformity of the synergistic effect between photocatalysis and plasma is achieved. Experimental results show that under the combined treatment conditions of photocatalysis and plasma, the virus inactivation efficiency is increased by 35.6% compared with the single treatment method, and the virus removal rate reaches 99.98%. At the same time, through the introduction of the intelligent feedback algorithm, the treatment efficiency is further increased by 12.7%.
[0097] 6. Technical effects and application prospects
[0098] The blood product virus inactivation system based on the synergistic effect of nano-catalytic photochemical inactivation and low-temperature plasma proposed in the present invention has the remarkable advantages of high efficiency, uniformity, and intelligent control. By optimizing different process parameters and introducing a dynamic feedback mechanism, the present invention can ensure the complete inactivation of viruses while maximizing the preservation of the biological activity and functional integrity of blood products. Experimental results show that under the condition of a 99.98% virus inactivation rate, the plasma protein activity retention rate is higher than 92.3%, and it is applicable to the virus inactivation treatment of different blood products (such as plasma, platelets, red blood cells, and immunoglobulins, etc.). In the future, this system can be widely applied to the production and safety management of blood products, providing a new technical path for improving the quality and safety of blood products.
[0099] The virus inactivation system for blood products based on the synergistic effect of nano-catalytic photochemistry inactivation and low-temperature plasma provided by the present invention realizes the efficient, uniform and precise inactivation of potential viruses in blood products through the integration of a nano-photocatalytic inactivation module, a low-temperature plasma inactivation module, a dynamic fluid stirring module and a sensing monitoring and intelligent feedback module. The synergistic effect of each module significantly improves the inactivation efficiency and safety, while ensuring that the biological activity of blood components is not damaged.
[0100] The nano-photocatalytic inactivation module is based on the photocatalytic properties of titanium dioxide (TiO2) and graphitic carbon nitride (g-C3N4) nano-materials. Under the irradiation of an LED light source in a specific wavelength range (365nm - 450nm), the nano-materials absorb light energy and generate electron-hole pairs (e - / h + ), thus triggering a series of redox reactions. In the presence of oxygen molecules and water molecules, highly reactive oxygen species (ROS) are formed, including hydroxyl radicals (·OH), superoxide anions (O2 - ·) and hydrogen peroxide (H2O2), etc. These highly reactive oxygen species attack the lipid membrane, nucleic acid (DNA / RNA) and structural proteins of the virus through oxidative stress reactions, thereby destroying the gene structure and protein function of the virus and achieving the inactivation effect. Compared with traditional photocatalytic materials, the composite system of TiO2 and g-C3N4 has a higher separation efficiency of photo-generated carriers and broad-spectrum response characteristics, thus significantly improving the inactivation efficiency and light energy utilization rate.
[0101] The low-temperature plasma inactivation module generates a plasma cloud in the surface area of the blood product through a low-temperature plasma generator, forming a complex gas phase environment containing a large number of high-energy electrons, ions, hydroxyl radicals (·OH) and reactive species (RS), etc. The high-energy particles generated in the plasma can directly damage the lipid bilayer membrane and nucleic acid molecules of the virus, and at the same time cooperate with the ROS generated by photocatalysis to enhance the destruction efficiency of the virus structure. In particular, the combined action of reactive nitrogen species (RNS) and ROS can effectively damage the protein coat and genetic material of the virus under relatively low temperature conditions, while avoiding the degradation and inactivation of blood components under high temperature conditions. The plasma generator ensures the efficiency and stability of the inactivation process by precisely controlling parameters such as voltage, frequency and gas flow rate.
[0102] To ensure the uniformity and efficiency of the inactivation process, the present invention adopts a microfluidic mixing technology to achieve dynamic stirring of blood products. The microfluidic device makes the blood evenly distributed in the photocatalysis and plasma treatment areas by designing a specific flow channel structure and flow velocity gradient. Through the combination of laminar-turbulent transition and tangential flow control, each component in the blood product can uniformly receive the action of highly reactive oxygen free radicals and reactive particles. This module not only improves the inactivation efficiency but also effectively reduces the problem of residual viruses caused by uneven local treatment. At the same time, the dynamic fluid stirring process can also avoid adverse phenomena such as precipitation and agglutination of blood products during the inactivation process, improving the stability and safety of the overall process.
[0103] In the present invention, through an integrated monitoring system of a spectral sensor and a biochemical sensor, the residual amount of virus nucleic acid, protein activity, and other key parameters in the blood are detected in real time. The spectral sensor identifies the structural changes of nucleic acid and protein during the virus inactivation process by detecting the absorption spectrum and fluorescence spectrum of specific wavelengths in the blood sample. The biochemical sensor measures the concentration of virus antigens or antibodies in the blood through electrochemical detection and enzyme-linked immunosorbent assay (ELISA). The collected data is input into the AI adaptive regulation algorithm module, which based on the combination of deep learning and fuzzy control algorithms, optimizes and adjusts the inactivation parameters in real time. Specifically, the AI algorithm dynamically adjusts the light intensity of the photocatalysis module, the power of the plasma module, and the inactivation time according to the real-time monitoring data and the preset target parameters to ensure the efficiency and uniformity of the virus inactivation process.
[0104] Through the synergistic effect of nano-photocatalytic inactivation and low-temperature plasma inactivation, the present invention significantly improves the virus inactivation efficiency and treatment uniformity. By introducing a dynamic fluid stirring module and an intelligent feedback regulation system, the accuracy and automation level of the treatment process are further improved. Compared with the prior art, the present invention can not only achieve efficient inactivation of viruses at a lower temperature but also optimize the treatment parameters through a real-time monitoring and intelligent regulation system, thereby ensuring the biological activity and safety of blood products after virus inactivation.
[0105] The main reaction equations of the nano-photocatalytic inactivation module 1 are as follows:
[0106] Electron transition of the photocatalyst:
[0107] TiO2+hv(λ=365nm - 450nm)→e - +h +
[0108] where, e - is a photo-generated electron, and h + is a hole;
[0109] Generation of reactive oxygen species (ROS):
[0110] O2+e - →O2 -
[0111] H2O+h + →OH·+H +
[0112] Superoxide anion (O2 - ·) and hydroxyl radicals (OH·) have extremely strong oxidizing ability and can degrade viral protein shells and RNA / DNA.
[0113] Virus inactivation process:
[0114] RNA / DNA+OH·→degradation products
[0115] Viral membrane protein + O2 - →Structural damage
[0116] These highly active oxidative species can destroy the nucleic acid chain of the virus, causing it to lose its ability to replicate, while also degrading the viral envelope protein, ultimately achieving the effect of inactivating the virus.
[0117] The key functions of the plasma in the low-temperature plasma deactivation module 2 are as follows:
[0118] (1) Generation of plasma active particles:
[0119] N2+e - →N2 * +e -
[0120] O2+e - →O2 - +O·
[0121] Among them, N2 * represents an excited nitrogen molecule, and O· represents a monatomic oxygen radical;
[0122] (2) Virus inactivation mechanism:
[0123] Protein denaturation: OH· and O· will destroy the viral membrane protein, making the virus unable to recognize host cells and lose its ability to infect;
[0124] RNA / DNA degradation: The high-energy electrons and superoxide anions released by plasma will directly attack viral nucleic acids, causing gene chain breaks and making the virus lose its ability to reproduce.
[0125] (3) Gentle treatment:
[0126] The temperature of low-temperature plasma does not exceed 40°C, which will not affect the protein activity in blood products and ensure safety.
[0127] As shown Figure 2 in the figure, the working mechanism of the dynamic fluid stirring module 3 is as follows:
[0128] (1) Microfluidic mixing
[0129] The blood product is made to flow in the inactivation chamber by a microfluidic pump and is fully contacted with the catalyst.
[0130] Adopting the laminar flow mixing principle, the fluid flow path is optimized to ensure the uniformity of virus inactivation.
[0131] (2) Electromagnetic stirring
[0132] An electromagnetic stirring device is adopted to generate a rotational flow inside the blood product, making the photocatalysis and plasma effects more uniform and improving the inactivation effect.
[0133] The working mechanism of the sensing monitoring and intelligent feedback module is as follows:
[0134] (1) Sensor monitoring
[0135] Spectral sensor: Real-time detection of virus nucleic acid content, fluorescence detection;
[0136] Biochemical sensor: Detection of blood component changes to ensure that the protein activity is not damaged;
[0137] (2) Intelligent AI regulation
[0138] An adaptive AI algorithm is adopted to analyze the data during the inactivation process and dynamically adjust the light intensity, plasma power, and inactivation time;
[0139] Through a PID closed-loop control system, the inactivation error is ensured to be controlled within ±1%.
[0140] As shown Figure 3 in the figure, an embodiment of the present invention provides a method for inactivating viruses in blood products based on the synergistic effect of nano-catalytic photochemical inactivation + low-temperature plasma of the blood product virus inactivation system based on nano-catalytic photochemical inactivation + low-temperature plasma. The method specifically includes:
[0141] S1: Pretreatment of blood products
[0142] Adopting a mild centrifugal separation technique, the blood products, such as plasma, red blood cells, and platelets, are fully mixed with virus contaminants to ensure uniform distribution; the blood pH value is adjusted to 7.2 - 7.4 to maintain the best virus inactivation effect.
[0143] S2: Nano-photocatalytic virus inactivation
[0144] Function of photocatalyst:
[0145] Add nano-photocatalytic material (TiO2 / g-C3N4) to blood products;
[0146] Irradiate with an LED light source (365 - 450 nm) to activate the photocatalyst and generate hydroxyl radicals (OH·), superoxide anions (O2 - ), singlet oxygen ( 1 O2);
[0147] These reactive oxygen free radicals can undergo oxidation reactions with viral proteins and nucleic acids, destroying the structure of the virus.
[0148] Dynamic fluid stirring:
[0149] Adopt microfluidic stirring technology to evenly distribute the photocatalyst in blood products, improving the virus inactivation efficiency;
[0150] S3: Synergistic inactivation by low-temperature plasma
[0151] Plasma generation:
[0152] Use a low-temperature plasma generator to form a plasma cloud above the blood products;
[0153] The low-temperature plasma releases high-energy electrons, ions, and OH· radicals, further destroying viral proteins and nucleic acids;
[0154] Dynamic feedback regulation:
[0155] Monitor the residual viral nucleic acid through a sensor, and intelligently control the intensity and action time of the plasma to ensure that the inactivation effect reaches over 99.99%;
[0156] S4: Post-treatment and quality inspection
[0157] Use biosensors and PCR technology to detect the residual virus, ensuring that the inactivation meets medical safety standards, such as FDA and WHO standards;
[0158] Detect the activity of blood proteins through ELISA to ensure that the inactivation process does not affect the quality of blood products.
[0159] The blood product virus inactivation system based on the synergistic effect of nano-catalytic photochemical inactivation + low-temperature plasma provided by the present invention utilizes the dual synergistic effect of photocatalytic oxidation (PCO) and low-temperature plasma (LTP) during the inactivation process of blood products to achieve efficient virus inactivation while maximizing the protection of the biological activity of blood products. The photocatalytic oxidation technology generates hydroxyl radicals (·OH), superoxide anions (O2 - ), singlet oxygen (1 O2), and these highly active oxides can rapidly oxidize viral proteins and nucleic acids, rendering them inactivated.
[0160] In the partial inactivation by low-temperature plasma synergism, a plasma cloud is formed around blood products by Gliding Arc Discharge. The plasma releases high-energy electrons, active ions, and short-wave ultraviolet radiation (UVC), and further promotes the generation of hydroxyl radicals (·OH) and hydrogen peroxide (H2O2). These active chemical species can penetrate deep into the blood products, irreversibly denature the secondary and tertiary structures of viral proteins, and degrade the viral genome, improving the uniformity of inactivation. Since the working temperature of low-temperature plasma does not exceed 40 °C, it avoids the damage to key components such as plasma proteins, coagulation factors, and immunoglobulins in blood products by traditional heat inactivation methods.
[0161] This system is equipped with an intelligent feedback control module, which integrates a virus nucleic acid detection sensor and an AI adaptive algorithm. It can detect the progress of virus inactivation in blood samples in real time and automatically adjust the concentration of photocatalyst, plasma intensity, and action time to ensure that the inactivation effect always remains above 99.99%. In addition, the system has a dynamic fluid stirring function, which optimizes the blood flow path through microfluidic mixing technology to avoid uneven inactivation caused by fluid stagnation or limited light penetration depth, thereby further improving the inactivation consistency.
[0162] In the post-inactivation treatment stage, the system uses a biosensor combined with PCR technology to accurately detect the residual amount of virus nucleic acid to ensure compliance with international medical safety standards such as the FDA (Food and Drug Administration of the United States) and the WHO (World Health Organization). At the same time, the system detects the retention rate of plasma proteins through ELISA (Enzyme-Linked Immunosorbent Assay) to ensure that the core functions of blood products are not affected during the virus inactivation process. Experimental data show that the method of the present invention can maintain the integrity of blood active components while the virus inactivation rate in blood products is ≥99.99%, which is significantly superior to the traditional solvent-detergent inactivation method (SD method) and the Pasteurization method.
[0163] This invention can be widely applied in fields such as clinical blood transfusion safety assurance, blood product production, blood disease treatment, and regenerative medicine. Especially when dealing with the transmission risks of infectious diseases (such as hepatitis B, hepatitis C, HIV, etc.), this technology can effectively improve the safety of blood products and reduce the possibility of transfusion-related virus transmission. In addition, this method can be used for the inactivation treatment of stem cell culture media, sera, and vaccine raw materials to meet the high standards of virus-free environment requirements in the fields of biopharmaceuticals and tissue engineering.
[0164] As described above, it is only the specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention, any modifications, equivalent substitutions and improvements made within the spirit and principle of the present invention shall be covered within the protection scope of the present invention.
Claims
1. A virus inactivation system for blood products based on the synergistic effect of nano-catalytic photochemistry inactivation + low-temperature plasma, characterized in that, The system includes: The nano-photocatalytic inactivation module uses titanium dioxide TiO2 and graphite phase carbon nitride g-C3N4 nanomaterials as photocatalysts. Under the irradiation of a specific wavelength 365nm-450nm LED, it produces highly reactive oxygen free radicals ROS, which destroy viral nucleic acids and protein structures. The low-temperature plasma inactivation module uses a low-temperature plasma generator to generate a plasma cloud above the blood product, releasing active particles, including electrons, ions, and hydroxyl radicals (OH·), which destroy viral membrane proteins and improve inactivation efficiency. The dynamic fluid stirring module uses microfluidic mixing technology to evenly inactivate blood products through photocatalysis and plasma, ensuring uniform viral inactivation. The sensor monitoring and intelligent feedback module uses spectral sensors and biochemical sensors to monitor the residual viral nucleic acid and protein activity in the blood in real time, and optimizes the inactivation parameters, including light intensity, plasma power, and time, through AI adaptive control algorithms.
2. The virus inactivation system for blood products based on the synergistic effect of nano-catalytic photochemistry inactivation + low-temperature plasma according to claim 1, characterized in that, The main reaction equation of the nano-photocatalytic deactivation module is as follows: Electronic transitions of photocatalysts: TiO2 + hv → e - + h + Among them, e - is the photo-generated electron, h + is the hole; Reactive oxygen radicals (ROS) production: O2+e - →O2 - H2O+h + →OH·+H + Superoxide anions and hydroxyl radicals have extremely strong oxidative ability and can degrade viral protein coats and RNA / DNA; Virus inactivation process: RNA / DNA+OH·→degradation products Viral membrane protein + O2 - → Structural damage These highly active oxidative species can destroy the nucleic acid chain of the virus, causing it to lose its ability to replicate, while also degrading the viral envelope protein, ultimately achieving the effect of inactivating the virus.
3. The viral inactivation system for blood products based on the synergistic effect of nano-catalytic photochemical inactivation + low-temperature plasma as claimed in claim 1, wherein, The key functions of the low-temperature plasma inactivation module plasma are as follows: (1) Generation of plasma active particles: N2 + e - → N2 * + e - O2+e - →O2 - +O· Among them, N2 * represents excited-state nitrogen molecules, and O· represents single-atom oxygen free radicals; (2) Virus inactivation mechanism: Protein denaturation: OH· and O· will destroy the viral membrane protein, making the virus unable to recognize host cells and lose its ability to infect; RNA / DNA degradation: The high-energy electrons and superoxide anions released by the plasma will directly attack the viral nucleic acid, causing the gene chain to break and the virus to lose its ability to reproduce; (3) Gentle treatment: The temperature of low-temperature plasma does not exceed 40°C, which will not affect the protein activity in blood products and ensure safety.
4. The virus inactivation system for blood products based on the synergistic effect of nano-catalytic photochemistry inactivation + low-temperature plasma as claimed in claim 1, wherein, The working mechanism of the dynamic fluid stirring module is as follows: (1) Microfluidic mixing The blood product is made to flow in the inactivation chamber by a microfluidic pump and fully contact with the catalyst; Adopting the laminar mixing principle, the fluid flow path is optimized to ensure uniform virus inactivation; (2) Electromagnetic stirring An electromagnetic stirring device is used to generate a rotating flow inside the blood product, making the photocatalytic and plasma effects more uniform and improving the inactivation effect.
5. The virus inactivation system for blood products based on the synergistic effect of nano-catalytic photochemistry inactivation + low-temperature plasma as claimed in claim 1, wherein, The working mechanism of the sensor monitoring and intelligent feedback module is as follows: (1) Sensor monitoring Spectral sensor: real-time detection of viral nucleic acid content, fluorescence detection; Biochemical sensors: detect changes in blood components to ensure protein activity is not damaged; (2) Intelligent AI Control Adopting adaptive AI algorithm to analyze data during the inactivation process and dynamically adjust light intensity, plasma power and inactivation time; The PID closed-loop control system ensures that the inactivation error is controlled within ±1%.
6. A method for inactivating viruses in blood products based on the synergistic effect of nano-catalytic photochemical inactivation + low-temperature plasma of a blood product virus inactivation system based on the synergistic effect of nano-catalytic photochemical inactivation + low-temperature plasma as described in claims 1-5, characterized in that, The method specifically includes: S1: Blood product pretreatment Adopt gentle centrifugation separation technology to fully mix blood products, such as plasma, red blood cells, and platelets, with virus contaminants to ensure uniform distribution; adjust the blood pH value to 7.2 - 7.4 to maintain the best virus inactivation effect; S2: Nano-photocatalytic virus inactivation Function of photocatalyst: Add nano-photocatalytic materials to blood products; Irradiate with an LED light source to activate the photocatalyst to generate hydroxyl radicals, superoxide anions, and singlet oxygen; These reactive oxygen free radicals can undergo oxidation reactions with virus proteins and nucleic acids to destroy the structure of the virus; Dynamic fluid stirring: Adopt microfluidic stirring technology to evenly distribute the photocatalyst in blood products and improve the virus inactivation efficiency; S3: Synergistic inactivation by low-temperature plasma Plasma generation: Adopt a low-temperature plasma generator to form a plasma cloud above the blood products; The low-temperature plasma releases high-energy electrons, ions, and OH· free radicals to further destroy virus proteins and nucleic acids; Dynamic feedback regulation: Monitor the residual virus nucleic acid through a sensor and intelligently control the intensity and action time of the plasma to ensure that the inactivation effect reaches more than 99.99%; S4: Post-treatment and quality inspection Adopt biosensors and PCR technology to detect the virus residue situation to ensure that the inactivation meets medical safety standards, such as FDA and WHO standards; Detect the activity of blood proteins through ELISA to ensure that the inactivation process does not affect the quality of blood products.
Citation Information
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