Method for connecting leukocyte-depleted filter and connecting pipe suitable for moist heat sterilization

Abstract

The invention belongs to the field of leukocyte-depleting filters, and particularly relates to a connecting method of a leukocyte-depleting filter and a connecting pipe suitable for moist heat sterilization. The invention aims to solve the technical problem that in the prior art, when a leukocyte-depleted filter is connected with a connecting pipe, due to the difference of thermal expansion coefficients of materials, interface stress concentration and damp-heat aging of an organic adhesive are caused, and then sealing failure, leakage or separation and the like occur after damp-heat sterilization. According to the connecting method for the leukocyte-depleted filter and the connecting pipe suitable for moist heat sterilization, the mechanical reliability of a connecting assembly is remarkably improved through the design of a composite interface of micro-bulge mechanical interlocking and hydrogel chemical bonding.

Description

Technical Field

[0001] This application belongs to the field of leukocyte filters, and particularly relates to a connection method between a leukocyte filter suitable for moist heat sterilization and a connecting tube. Background Art

[0002] In the field of clinical transfusion medicine, leukocyte filters, as the core devices to ensure the safety of blood products, undertake the key function of removing leukocytes. Their working principle is based on a precise multi-layer filter membrane structure. By physically sieving pores, more than 99.9% of the leukocytes in whole blood or component blood are intercepted, while allowing effective components such as red blood cells and platelets to pass through. This filtering mechanism can remove lymphocytes, reduce the incidence of graft-versus-host disease, reduce the exposure of leukocyte antigens, avoid transfusion adverse reactions such as fever and allergy caused by alloimmune reactions, inhibit the release of leukocyte-derived inflammatory factors, and reduce the risk of transfusion-related acute lung injury. To meet the aseptic requirements, the filter needs to be integrally sterilized by moist heat after being integrated with the PVC blood transfusion pipeline, which poses a severe challenge to the connection reliability between the filter and the pipeline.

[0003] Currently, the existing technology generally adopts an adhesive solution. This technology fixes the filter interface made of polypropylene (PP) and the polyvinyl chloride (PVC) pipeline through epoxy adhesive, and uses the mechanical strength after the curing of the adhesive layer to achieve sealing. However, when this component undergoes moist heat sterilization, the inherent differences in the thermophysical properties of the materials trigger a chain of failures. The thermal expansion coefficient of polypropylene is quite different from that of polyvinyl chloride, and the shear stress generated at the adhesive layer interface due to this expansion difference far exceeds the yield strength of epoxy resin. The chemical aging of epoxy resin adhesive in a moist heat environment further exacerbates the vulnerability of the system. High temperature and high humidity conditions prompt the hydrolysis and breakage of the ester bonds in the epoxy molecular chain, and its reaction rate increases exponentially with temperature. Even if the component is placed back in a dry environment, the broken molecular chains cannot spontaneously reconstruct. In the face of the inherent defects of the adhesive technology, the industry has tried to develop alternative connection solutions. Ultrasonic welding attempts to achieve interlayer fusion of PP and PVC molecules through high-frequency vibration. However, the melting temperature of PP is significantly lower than that of PVC. When the energy input is sufficient to soften PVC, PP is already in a state of over-melting. This results in a large number of unfused pores in the welding area, and this structural defect leads to a reduction in strength. When the blood bag is subjected to extrusion and impact during transportation, the interface is extremely prone to rupture.

[0004] The failure modes of the existing technology can be summarized into two interrelated contradictions: First, the problem of interfacial stress concentration caused by the difference in thermal expansion coefficients of materials. Second, the problem of moist heat aging of organic adhesives. Although epoxy resin provides good sealing effect at room temperature, its molecular structure will inevitably degrade in a high temperature and high humidity environment. How to construct a connection system that can withstand repeated moist heat sterilization is a common problem that the existing technology urgently needs to break through. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to overcome the problems in the prior art that when a leukocyte filter is connected to a connecting tube, due to the difference in the coefficient of thermal expansion of materials, interface stress concentration occurs, and the organic adhesive undergoes hygrothermal aging, resulting in seal failure, leakage or separation after moist heat sterilization. A connection method for a leukocyte filter and a connecting tube suitable for moist heat sterilization is provided to improve the connection reliability and the finished product rate.

[0006] The present application provides a connection method for a leukocyte filter and a connecting tube suitable for moist heat sterilization, comprising the following steps:

[0007] S1. Laser engrave a micro-protrusion array at 2-3 mm from the root of the thread of the PC connector;

[0008] S2. Precoat a polyacrylamide hydrogel layer containing nano-SiO₂ in the socket groove of the PC connector;

[0009] S3. Make the PP interface of the leukocyte filter and the PC connector in interference fit by thread, apply an axial pressure to make the PP cold flow fill the micro-protrusion gap, and keep the pressure;

[0010] S4. Flare the end of the PVC connecting tube, after heating the end of the PC connector to 145-155 °C and the end of the PVC connecting tube to 160-170 °C by laser, apply a pressing force to make the PC connector and the PVC connecting tube press-fit and interlock, and air-cool after pressing to obtain an assembly;

[0011] S5. Keep the assembly obtained in S4 in a hot air environment at 80-90 °C for 25-35 minutes.

[0012] Furthermore, the height of the micro-protrusions is 50-100 μm, and the spacing is 0.3-0.8 mm.

[0013] Furthermore, the hydrogel uses bisacrylated polytetrahydrofuran as a crosslinking agent, the molar ratio of bisacrylated polytetrahydrofuran to acrylamide is 1:28 - 1:32, the concentration of the initiator ammonium persulfate is 0.1-0.3 mol%, and it is polymerized at 55-65 °C for 1.5-2.5 h to form, the mass fraction of nano-SiO₂ is 15% - 20%, and the pre-cured thickness at 55-65 °C is 180-220 μm.

[0014] Furthermore, the interference amount at room temperature in step S3 is 0.05-0.1 mm, apply an axial pressure of 6±0.5 N to make the PP cold flow fill the micro-protrusion gap, and keep the pressure for 30±5 seconds.

[0015] Furthermore, the polyacrylamide hydrogel layer is secondarily crosslinked by an aqueous glutaraldehyde solution, the concentration of the aqueous glutaraldehyde solution is 5-10 wt%, and the soaking time is 25-35 minutes.

[0016] Furthermore, the micro-protrusions are processed using a 1064 nm wavelength fiber laser with a power of 20 - 30 W and a pulse frequency of 18 - 22 kHz.

[0017] In this application, diacrylated polytetrahydrofuran is used as a long-chain crosslinking agent and mixed with acrylamide (AM). Ammonium persulfate is added as an initiator, and a three-dimensional covalent network is formed through a free radical polymerization reaction. Diacrylated polytetrahydrofuran is a functional polymer with acryloyl groups modified at both ends. Its molecular structure has polytetrahydrofuran diol as a flexible backbone, and two acryloyl groups serve as free radical polymerization reaction sites, which are anchored on the polymer network through covalent bonds to form long-chain crosslinking points. The long-chain structure of diacrylated polytetrahydrofuran significantly increases the network pore size, forming a loose porous structure, endowing the hydrogel with a high elongation at break and greatly improving its swelling ratio. The long-chain structure of diacrylated polytetrahydrofuran forms a large-pore covalent network during the polymerization process. The distance between molecular chains is relatively large, allowing the chain segments to undergo significant slippage and conformational changes under external forces instead of direct fracture. Compared with the tight network formed by traditional short-chain crosslinking agents, the flexibility of the long-chain network significantly enhances the deformation ability.

[0018] The initial hydrogel is immersed in an aqueous solution of glutaraldehyde (GA), and dynamic imine bonds are introduced through the Schiff base reaction between aldehyde groups and amide groups. This bond has the characteristics of reversible fracture and recombination, stably exists at room temperature, and provides structural strength. When the temperature rises or the strain increases, the bond energy is insufficient to resist the external force, and reversible fracture occurs, releasing the interfacial stress. After the stress is eliminated, the imine bond can be re-formed. It can provide a fracture strength greater than 150 kPa at room temperature, and the retention rate of the repeat performance under tensile or compressive strain is greatly improved. Under high-temperature or high-strain conditions, it can dynamically release stress, effectively buffering the thermal expansion difference between PP and PC / PVC, and avoiding interfacial cracking caused by stress concentration.

[0019] 15% - 20% by mass fraction of nano-SiO₂ is added to the hydrogel. The hydroxyl groups on the surface of SiO₂ form hydrogen bonds with the hydrogel segments, increasing the crosslinking density. The rigid particles bear part of the tensile load, inhibiting crack propagation. Its high thermal stability inhibits the degradation of the hydrogel molecular chains at high temperatures, enhancing the mechanical strength and heat resistance. The hydrogel containing nano-SiO₂ is pre-coated in the socket groove of the PC connector and pre-cured at 60 °C to a thickness of 180 - 220 μm to form an interfacial layer with both viscosity and elasticity.

[0020] This application uses a fiber laser to engrave a truncated cone-shaped micro-protrusion array with a height of 50 to 100 μm and a spacing of 0.3 to 0.8 mm on the root of the thread of the PC connector. The thermal effect of the laser engraving causes the PC surface to melt locally and then solidify rapidly, forming regularly arranged micro-protrusions, whose cross-sectional area gradually decreases along the depth direction, optimizing the cold flow filling effect of the PP interface. The height of the micro-protrusion matches the depth of the PP cold flow, forming a microscopic "sawtooth" interface. After the PP cold flow fills the gap between the micro-protrusions, the interface destruction needs to overcome the mechanical blocking force of the micro-protrusions and the cohesive strength and interfacial adhesion of the hydrogel at the same time. The shear strength of this composite interface far exceeds that of traditional epoxy resin bonding processes.

[0021] The PP interface of the leukocyte depletion filter is screwed together with the PC connector with a room-temperature interference fit of 0.05-0.1mm. An axial pressure of 6±0.5N is applied and maintained for 30±5 seconds. Under pressure, the PP material undergoes cold flow deformation, filling the gaps between the microprotrusions and the micropores of the hydrogel layer, forming a dual interface of mechanical interlocking and chemical bonding. The geometric blocking force of the microprotrusions and the adhesive force of the hydrogel synergistically increase the interfacial shear strength to 3-5 times that of traditional adhesive bonding. After flaring the PVC ends, laser heating is used to raise the temperature of the PC connector to 145-155°C and the PVC end to 160-170°C. At this point, the hydrogel layer enters a highly elastic state, enhancing its fluidity and filling the microscopic defects at the PC-PVC interface. The PVC material softens but does not melt, interlocking with the PC component under a compression force of 40-60N. After air cooling to below 80°C, the dynamic imine bonds in the hydrogel layer resolidify, forming a stable connection.

[0022] The beneficial effects of this application are:

[0023] 1. Traditional epoxy resin adhesives rely on ester crosslinking, which is prone to hydrolysis and fracture in high-temperature and high-humidity environments, causing the adhesive layer to gradually become brittle from an elastic state to a glassy state, eventually cracking and falling off. However, the polyacrylamide hydrogel used in the present invention introduces dynamic imine bonds through secondary crosslinking with glutaraldehyde. After undergoing moist heat sterilization, the hydrogel interface still maintains a high fracture strength retention rate. In addition, the reversible stress response mechanism of the dynamic imine bond can actively buffer the thermal expansion difference of the material. When PP and PVC produce an expansion difference due to temperature changes, the imine bond can dynamically break and release interfacial shear stress, avoiding structural damage caused by stress concentration.

[0024] 2. This invention significantly enhances the mechanical reliability of the connected components through a composite interface design combining mechanical interlocking of microprotrusions with chemical bonding of hydrogel. The laser-engraved microprotrusion array and the cold flow of the PP interface form a microscopic, serrated interlocking structure. Combined with the viscous adsorption of the hydrogel layer, this significantly increases the overall shear strength, surpassing that of traditional epoxy resin bonding by 3-5 times. This strength is sufficient to withstand the tensile forces commonly encountered in clinical operations, such as the traction and impact forces during blood bag handling, reducing the risk of leakage.

[0025] 3. The polyacrylamide hydrogel adopts a solvent-free polymerization process and does not use volatile organic compounds throughout the process, avoiding the potential pollution risk of traditional epoxy resin adhesives solvents such as benzyl alcohol and acetone residues to blood products. The dynamic imine bond cross-linking process does not require additional catalysts, reducing the generation of chemical waste compared with the two-component mixing process of epoxy resin. The hydrogel layer can be physically recycled, such as solvent swelling regeneration and reused, which conforms to the concept of circular economy. For medical waste treatment, the biodegradability of the hydrogel is also significantly better than the difficult-to-degrade characteristics of epoxy resin, further reducing the environmental burden. Detailed implementation manners

[0026] In order to make the present invention easier to understand, the embodiments of the present invention will be further elaborated below. The present invention will be further described and demonstrated in combination with the embodiments, but these embodiments do not limit the present invention. The technical solutions described in the present invention are all conventional solutions in the art unless otherwise specified; the reagents or materials shown are all from commercial channels unless otherwise specified.

[0027] The structure of the leukocyte filter described in this application is described in detail in Chinese Patent No. 202521052613X.

[0028] Example 1

[0029] S1. Use an IPG YLP-1-100-20-20 fiber laser, set the parameters of power 20W, frequency 18.0kHz, and scanning speed 120mm / s, and process a micro-protrusion array with a height of 50±3μm and a pitch of 0.80mm at the root of the thread of the PC connector.

[0030] S2. Dehydrate 50g of polytetrahydrofuran diol under a vacuum of -0.1MPa and at 90°C for 2 hours to completely remove moisture. After dehydration, cool the system to 0°C, add 150mL of anhydrous dichloromethane, slowly dropwise add a mixed solution of acryloyl chloride and triethylamine, control the temperature ≤5°C, and raise the temperature to 25°C after dropping and react for 12 hours. The molar ratio of polytetrahydrofuran diol to acryloyl chloride and triethylamine is 1:2.2:2.5. After washing and drying, obtain bis-acrylated polytetrahydrofuran; add 3.2g of bis-acrylated polytetrahydrofuran, 86.8g of acrylamide, 0.11g of 0.1mol% ammonium persulfate, and 16.5g of nano-SiO2 to polymerize in a water bath at 60.0±0.5°C for 150min; use an EFD 781 dispensing machine to spray in the PC socket groove, cure in an oven at 60°C, with a thickness of 182μm, and then soak in a 5.0wt% glutaraldehyde solution for 35min and rinse with deionized water 3 times.

[0031] S3. Screw the filter PP interface onto the PC part, with an interference fit of 0.052mm, apply an axial pressure of 5.48±0.05N, and maintain the pressure for 35.0s.

[0032] For the end of the S4.PVC pipe, it is flared with a taper die. The Rofin DL0310S laser heats the PC end to 145 ± 1.2 °C and the PVC end to 161 ± 2.1 °C. The SMC pneumatic press maintains a pressing force of 55.2 ± 0.8 N for 5.0 s, with an air cooling rate of 4.2 m / s, and cools to 40 °C.

[0033] S5. The oven is maintained at 80 °C for 35.0 min.

[0034] Example 2

[0035] S1. Use an IPG YLP-1-100-20-20 fiber laser, with the parameter settings of power 30 W, frequency 22.0 kHz, and scanning speed 80 mm / s, to process a micro-protrusion array with a height of 100 ± 4 μm and a pitch of 0.302 mm at the thread root of the PC connector.

[0036] S2. Dehydrate 50 g of polytetrahydrofuran diol under -0.1 MPa vacuum and at 90 °C for 2 hours to completely remove moisture. After dehydration, cool the system to 0 °C, add 150 mL of anhydrous dichloromethane, slowly dropwise add a mixed solution of acryloyl chloride and triethylamine, control the temperature ≤ 5 °C, and after dropping, raise the temperature to 25 °C and react for 12 hours. The molar ratio of polytetrahydrofuran diol to acryloyl chloride and triethylamine is 1:2.2:2.5. After washing and drying, obtain bis-acrylated polytetrahydrofuran; polymerize 4.8 g of bis-acrylated polytetrahydrofuran, 85.2 g of acrylamide, 0.32 g of 0.3 mol% ammonium persulfate, and 22.0 g of nano-SiO₂ in a 55 °C water bath for 90.0 min; use an EFD 781 dispensing machine to spray in the PC socket groove, cure in a 55 °C oven, with a thickness of 217 μm, then soak in a 10.0 wt% glutaraldehyde solution for 25 min, and rinse with deionized water 3 times.

[0037] S3. The PP interface of the filter is screwed onto the PC part with an interference amount of 0.098 mm, and an axial pressure of 6.52 ± 0.07 N is applied and held for 25.0 s.

[0038] S4. After the PVC pipe is flared, the Rofin DL0310S laser heats the PC end to 155 ± 1.5 °C and the PVC end to 169 ± 2.3 °C. The SMC pneumatic press maintains a pressing force of 60.3 ± 0.9 N for 5.0 s, and cools to 40 °C at an air cooling rate of 4.5 m / s.

[0039] S5. The oven is maintained at 90 °C for 25 min.

[0040] Example 3

[0041] S1. Use an IPG YLP-1-100-20-20 fiber laser, set the parameters of power at 25 W, frequency at 20 kHz, and scanning speed at 100 mm / s, and process a micro-protrusion array with a height of 74 ± 3 μm and a pitch of 0.55 mm at the root of the thread of the PC connector.

[0042] S2. Dehydrate 50 g of polytetrahydrofuran diol under -0.1 MPa vacuum at 90 °C for 2 hours to completely remove moisture. After dehydration, cool the system to 0 °C, add 150 mL of anhydrous dichloromethane, and slowly dropwise add a mixed solution of acryloyl chloride and triethylamine while controlling the temperature ≤ 5 °C. After dropping, raise the temperature to 25 °C and react for 12 hours. The molar ratio of polytetrahydrofuran diol to acryloyl chloride and triethylamine is 1:2.2:2.5. After washing and drying, obtain bis-acrylated polytetrahydrofuran. Polymerize 4.0 g of bis-acrylated polytetrahydrofuran, 86.0 g of acrylamide, 0.22 g of 0.2 mol% ammonium persulfate, and 19.8 g of nano-SiO₂ in a water bath at 60.0 ± 0.5 °C for 150 min. Spray in the PC socket groove using an EFD 781 dispenser, cure in an oven at 60 °C, with a thickness of 201 μm, then soak in a 7.5 wt% glutaraldehyde solution for 35 min, and rinse with deionized water 3 times.

[0043] S3. Screw the PP interface of the filter onto the PC part with an interference fit of 0.075 mm, apply an axial pressure of 6.03 ± 0.05 N, and keep the pressure for 30.0 s.

[0044] S4. Flare the end of the PVC pipe with a taper die. Heat the PC end to 150 ± 1.2 °C and the PVC end to 165 ± 2.1 °C with a Rofin DL0310S laser. The SMC pneumatic press maintains a pressing force of 58.1 ± 0.8 N for 5.0 s, with an air cooling rate of 4.2 m / s, and cool to 40 °C.

[0045] S5. Maintain in an oven at 80 °C for 35 min.

[0046] In Comparative Example 1, the setting of the micro-protrusion array was removed, and the rest was the same as in Example 3.

[0047] S1. Dehydrate 50 g of polytetrahydrofuran diol under -0.1 MPa vacuum at 90 °C for 2 hours to completely remove moisture. After dehydration, cool the system to 0 °C, add 150 mL of anhydrous dichloromethane, and slowly dropwise add a mixed solution of acryloyl chloride and triethylamine while controlling the temperature ≤ 5 °C. After dropping, raise the temperature to 25 °C and react for 12 hours. The molar ratio of polytetrahydrofuran diol to acryloyl chloride and triethylamine is 1:2.2:2.5. After washing and drying, obtain bisacrylated polytetrahydrofuran; polymerize 4.0 g of bisacrylated polytetrahydrofuran, 86.0 g of acrylamide, 0.22 g of 0.2 mol% ammonium persulfate, and 19.8 g of nano-SiO₂ in a water bath at 60.0 ± 0.5 °C for 150 min; spray using an EFD 781 dispensing machine in the PC socket groove, cure in an oven at 60 °C, with a thickness of 201 μm, and then soak in a 7.5 wt% glutaraldehyde solution for 35 min and rinse 3 times with deionized water.

[0048] S2. Screw the PP interface of the filter onto the PC part with an interference fit of 0.075 mm, apply an axial pressure of 6.03 ± 0.05 N, and maintain the pressure for 30.0 s.

[0049] S3. Flare the end of the PVC pipe with a taper die. Heat the PC end to 150 ± 1.2 °C and the PVC end to 165 ± 2.1 °C with a Rofin DL0310S laser. The SMC pneumatic press maintains a pressing force of 58.1 ± 0.8 N for 5.0 s, with an air cooling rate of 4.2 m / s, and cool to 40 °C.

[0050] S4. Maintain in an oven at 80 °C for 35.0 min.

[0051] For Comparative Example 2, the hydrogel is not cross-linked for the second time, and the rest is the same as in Example 3.

[0052] S1. Use an IPG YLP-1-100-20-20 fiber laser, set the parameters of power 25 W, frequency 20 kHz, and scanning speed 100 mm / s, and process a micro-protrusion array with a height of 74 ± 3 μm and a pitch of 0.55 mm at the root of the thread of the PC connector.

[0053] S2. Dehydrate 50 g of polytetrahydrofuran diol under -0.1 MPa vacuum at 90 °C for 2 hours to completely remove moisture. After dehydration, cool the system to 0 °C, add 150 mL of anhydrous dichloromethane, and slowly dropwise add a mixed solution of acryloyl chloride and triethylamine while controlling the temperature ≤ 5 °C. After dropping, raise the temperature to 25 °C and react for 12 hours. The molar ratio of polytetrahydrofuran diol to acryloyl chloride and triethylamine is 1:2.2:2.5. After washing and drying, obtain bisacrylated polytetrahydrofuran; polymerize 4.0 g of bisacrylated polytetrahydrofuran, 86.0 g of acrylamide, 0.22 g of 0.2 mol% ammonium persulfate, and 19.8 g of nano-SiO₂ in a water bath at 60.0 ± 0.5 °C for 150 min; use an EFD 781 dispensing machine to spray in the PC socket groove and cure in an oven at 60 °C with a thickness of 201 μm.

[0054] S3. Screw the PP interface of the filter onto the PC part with an interference fit of 0.075 mm, apply an axial pressure of 6.03 ± 0.05 N, and maintain the pressure for 30.0 s.

[0055] S4. Flare the end of the PVC pipe with a taper mold. Heat the PC end to 150 ± 1.2 °C and the PVC end to 165 ± 2.1 °C with a Rofin DL0310S laser. The SMC pneumatic press maintains a pressing force of 58.1 ± 0.8 N for 5.0 s with an air cooling rate of 4.2 m / s and cools to 40 °C.

[0056] S5. Maintain in an oven at 80 °C for 35.0 min.

[0057] In Comparative Example 3, a traditional binder was used to replace the hydrogel, and the rest was the same as in Example 3.

[0058] S1. Use an IPG YLP-1-100-20-20 fiber laser with parameters set as power 25 W, frequency 20 kHz, and scanning speed 100 mm / s to machine a micro-protrusion array with a height of 74 ± 3 μm and a pitch of 0.55 mm at the root of the thread of the PC connector.

[0059] S2. Apply LOCTITE MED4860 medical-grade two-component epoxy resin in the PC socket groove.

[0060] S3. Screw the PP interface of the filter onto the PC part with an interference fit of 0.075 mm, apply an axial pressure of 6.03 ± 0.05 N, and maintain the pressure for 30.0 s.

[0061] S4. Flare the end of the PVC pipe with a taper mold. Heat the PC end to 150 ± 1.2 °C and the PVC end to 165 ± 2.1 °C with a Rofin DL0310S laser. The SMC pneumatic press maintains a pressing force of 58.1 ± 0.8 N for 5.0 s with an air cooling rate of 4.2 m / s and cools to 40 °C.

[0062] S5. The oven is maintained at 80 °C for 35.0 min.

[0063] The following performance tests were carried out on the examples and comparative examples, and the test results are shown in Table 1;

[0064] 1. Damp heat sterilization durability test: Twenty assemblies were placed in a Getinge 8666 sterilizer and sterilized with saturated steam at 121 °C for 30 minutes. After cooling, visual inspection and fluorescein leakage detection were carried out: The 0.1 g / L fluorescein solution was pressurized to 120 kPa and kept under pressure for 5 minutes. Five sterilization cycles were repeated, and the number of leaking products was recorded.

[0065] 2. Interface shear strength test: The connection interface between the PP interface of the leukocyte filter and the PC connector was cut into 10 mm × 10 mm specimens, and a shear force was applied at a speed of 1 mm / min using an Instron 5944 universal testing machine, and the force value mutation point was recorded.

[0066] 3. Interface tensile strength test: The two ends of the PP interface of the leukocyte filter and the PC connector were fixed to an Instron 5944 universal testing machine, and an axial tensile force was applied at a speed of 20 mm / min, and the maximum load at the separation of the connection was recorded.

[0067] Table 1: Performance test results

[0068] Number of sterilization leakage products Tensile strength / N Shear strength / MPa Example 1 0 40.3 4.12 Example 2 0 38.6 4.63 Example 3 0 43.7 4.82 Comparative example 1 20 13.2 1.21 Comparative example 2 20 27.5 2.35 Comparative example 3 20 17.5 0.79

[0069] The examples maintained a zero leakage record throughout 15 consecutive sterilization cycles at 121 °C, demonstrating that the micro-protrusion structure and the secondary cross-linked hydrogel can provide stable sealing. In Comparative Example 1, 12 leaks occurred after the first sterilization, and all failed by the third sterilization. The interface of the failed parts showed a smooth separation state. Without micro-protrusions, a single hydrogel layer could not resist the interfacial slip caused by thermal expansion. In Comparative Example 2, there was no leakage in the first sterilization, but all leaked suddenly during the third sterilization. The swelling rate of the hydrogel increased sharply from the initial 120% to 280%. After dehydration and shrinkage, a crack network was formed, and the missing imine bonds prevented the molecular chains from recombining, resulting in the disintegration of the gel network under alternating wet and heat conditions. In Comparative Example 3, 15 leaks occurred after 3 sterilizations, the ester bonds in the adhesive layer were hydrolyzed at 121 °C, and the interfacial peel strength decreased.

Claims

1. A connection method for a leukocyte filter and a connecting tube suitable for moist heat sterilization, characterized in that, It includes the following steps: S1. Laser engrave a micro-protrusion array at 2-3 mm from the thread root of the PC connector; S2. Precoat a polyacrylamide hydrogel layer containing nano-SiO2 in the socket groove of the PC connector; S3. Make the PP interface of the leukocyte filter and the PC connector in interference fit by thread, apply axial pressure to make the PP flow cold to fill the micro-protrusion gaps, and keep the pressure; S4. Flare the end of the PVC connecting pipe, after heating the end of the PC connector to 145-155 °C and the end of the PVC connecting pipe to 160-170 °C by laser, apply a pressing force to make the PC connector and the PVC connecting pipe press-fit and interlock, and air-cool after pressing to obtain an assembly; S5. Maintain the assembly obtained in S4 in a hot air environment at 80-90 °C for 25-35 minutes.

2. The connection method of the leukocyte filter applicable to moist heat sterilization and the connecting pipe according to claim 1, characterized in that: The height of the micro-protrusions is 50-100 μm and the spacing is 0.3-0.8 mm.

3. The connection method of the leukocyte filter applicable to moist heat sterilization and the connecting pipe according to claim 1, characterized in that: The hydrogel uses bisacrylated polytetrahydrofuran as a crosslinking agent, the molar ratio of bisacrylated polytetrahydrofuran to acrylamide is 1:28 - 1:32, the concentration of initiator ammonium persulfate is 0.1-0.3 mol%, polymerizes at 55-65 °C for 1.5-2.5 h to form, the mass fraction of nano-SiO2 is 15% - 20%, and the pre-cured thickness at 55-65 °C is 180-220 μm.

4. The connection method of the leukocyte filter applicable to moist heat sterilization and the connecting pipe according to claim 1, characterized in that: In step S3, the interference amount at room temperature is 0.05-0.1 mm, apply an axial pressure of 6±_{0.5} N to make the PP flow cold to fill the micro-protrusion gaps, and keep the pressure for 30±5 seconds.

5. The connection method of the leukocyte filter applicable to moist heat sterilization and the connecting pipe according to claim 3, characterized in that: The polyacrylamide hydrogel layer is secondarily crosslinked by an aqueous glutaraldehyde solution, the concentration of the aqueous glutaraldehyde solution is 5-10 wt%, and the soaking time is 25-35 minutes.

6. The connection method of the leukocyte filter applicable to moist heat sterilization and the connecting pipe according to claim 1, characterized in that: The micro-protrusions are processed using a fiber laser with a wavelength of 1064 nm, a power of 20-30 W, and a pulse frequency of 18-22 kHz.