Preparation process of transparent bag for cell resuscitation

Abstract

The invention discloses a preparation process of a transparent bag for cell resuscitation, which comprises the following steps of: 1, preparing raw materials: selecting FEP (Fluorinated Ethylene Propylene) particles meeting the biocompatibility requirement as a main raw material, and preferentially selecting a medical-grade raw material with the purity of more than or equal to 99.9 percent; after the raw materials are selected, FEP particles are put into a vacuum drying oven and dried for 4-6 hours under the conditions that the temperature is 80-100 DEG C and the vacuum degree is smaller than or equal to-0.09 MPa, residual moisture in the raw materials is removed, and the situation that bubbles are generated during extrusion to affect the quality of the thin film is avoided; and 2, hot melting and film pressing: putting the FEP particles dried in the step 1 into an extruder, and melting the FEP particles. Then, the molten FEP is extruded into a film shape through an extruding machine head, the film is subjected to thickness adjustment and surface flattening treatment through a calendering device, and an FEP film with a certain thickness and width is prepared; according to the invention, FEP particles are pretreated, and then five-stage gradient temperature degradation and three-stage cooling of the extruder are carried out, so that the prepared film is uniform and smooth, and the rejection rate is reduced.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of cell resuscitation transparent bag, in particular to a preparation process of a cell resuscitation transparent bag. BACKGROUND

[0002] In the field of biological medicine and cell engineering, low-temperature storage and resuscitation of cells are key links to ensure cell activity, promote cell therapy, drug research and development, and basic research. The safety, stability and adaptability of the container during the cell resuscitation process are extremely high, which needs to ensure that the container does not break in the-196℃ liquid nitrogen low-temperature environment, no harmful substances are dissolved in contact with the cells and the culture solution, has good transparency to observe the cell state, and can conveniently cooperate with the resuscitation operation to realize liquid addition and transfer. The cell resuscitation transparent bag as an ideal cell resuscitation container plays an important role in the safe resuscitation of cells. However, the overall preparation process of the current cell resuscitation transparent bag is relatively traditional, and the hot melting treatment of the raw material is controlled by a single temperature during preparation. The overall quality of the prepared raw material is poor, which reduces the yield of the cell resuscitation transparent bag. Therefore, a new preparation process is needed to improve the yield of the cell resuscitation transparent bag. SUMMARY

[0003] The present application aims to provide a preparation process of a cell resuscitation transparent bag to solve the problems in the background art.

[0004] To achieve the above-mentioned purpose, the present application provides the following technical solution: a preparation process of a cell resuscitation transparent bag, comprising the following steps: First step, preparation of raw materials: select FEP particles meeting the biological compatibility requirements as the main raw material, and preferentially select medical-grade raw materials with a purity of 99.9% or more; After selecting the raw material, the FEP particles are placed in a vacuum drying oven and dried at 80-100℃ and a vacuum degree of-0.09MPa or less for 4-6 hours to remove the residual moisture in the raw material and avoid the generation of bubbles during extrusion to affect the film quality; Second step, hot melting and film pressing: the dried FEP particles in the first step are put into an extruder to melt the FEP particles. Then the melted FEP is extruded into a film shape through the extruder head, and the film is subjected to thickness adjustment and surface smoothing treatment by a calendering device to form a FEP film with a certain thickness and width; Third step, cutting and forming: the FEP film obtained in the second step is subjected to cooling treatment to cool and shape the FEP film, and then a numerical control laser cutting machine is used to cut the shaped FEP film; Fourth step, heat sealing: a pulse heat sealer is used to heat seal the edges of the FEP film cut in the third step to form the shape of the bag body; Fifth step, accessory assembly: assemble the luer joint with the FEP bag body processed in the fourth step, thereby forming a preliminary cell recovery transparent bag; Sixth step, sterilization treatment: finally, the preliminary cell recovery transparent bag is placed in a gamma ray sterilizer for sterilization treatment. The sterilized bag body is cooled to room temperature (23±2℃) in a ten-thousand-level clean workshop, and then sealed and packaged, thereby preparing a cell recovery transparent bag.

[0005] Preferably, the first step is followed by a screening process after the dry treatment of FEP particles. The screening process passes through two levels of screening devices. The first level is a 100-mesh vibrating screen to remove large particle impurities, and the second level is a magnetic screening to remove metal debris, ensuring that there are no impurities with a particle size of ≥50 μm in the raw material, preventing pinholes and defects in the film.

[0006] Preferably, the extruder barrel in the hot melt film pressing process is divided into five temperature zones, with a temperature gradient from the feeding port to the die head set as: 260℃→280℃→300℃→310℃→305℃, allowing the FEP particles to melt gradually.

[0007] Preferably, the extruder head uses a T-shaped flat film die head, with a die gap of 50-100 μm according to the target film thickness, a gap deviation of ≤±2 μm, and a polished die surface with a roughness Ra≤0.02 μm.

[0008] Preferably, the extruder extrudes the FEP particles, and then the extruded raw material is subjected to calendering treatment. The calendered film enters the cooling channel, which adopts a three-stage cooling: first stage 200℃→second stage 150℃→third stage 80℃, with a cooling air speed controlled at 2-3 m / s, ensuring that the film is quickly shaped and has no internal stress residue. The cooled film is transported to the winding device by the traction roller, with a winding tension set at 50-80 N to avoid film wrinkles.

[0009] Preferably, the wavelength of the numerical control laser cutting machine is 1064 nm, the cutting path is set according to the bag size, the cutting speed is controlled at 10-15 mm / s, and the laser power is adjusted to 30-50 W, ensuring that the burr height of the cut is ≤0.1 mm.

[0010] Preferably, the heat sealing head of the pulse heat sealer is made of polytetrafluoroethylene, with a flatness of ≤0.01 mm. The heat sealing temperature for a 50 μm film is 260-270℃, the pressure is 0.3-0.5 MPa, and the heat sealing time is 3-5 s.

[0011] Preferably, the luer joint is smoothed before assembly, with a roughness Ra≤0.1 μm, to avoid scratching the bag body or residual cells, and then subjected to gamma ray pre-sterilization with a sterilization dose of 25-30 kGy.

[0012] Preferably, the luer joint is assembled with the FEP bag body, and the film at the opening of the FEP bag body is heated to a softened state, the heating temperature is 200-220 DEG C, the heating time is 1-2 s, after heating, the luer joint is inserted, axial pressure of 5-8 kN is applied by a crimping tool, and the joint is combined with the bag body tightly for 10-15 s.

[0013] Compared with the prior art, the present application has the following beneficial effects: The preparation process of the cell resuscitation transparent bag is characterized in that the FEP particles are pretreated, and then heated by a five-stage gradient temperature of an extruder and cooled by a three-stage cooling, so that the prepared film sheet is uniform and smooth, and the waste rate is reduced. BRIEF DESCRIPTION OF DRAWINGS

[0014] Fig. 1 The figure is a flowchart of the present application; Fig. 2 The figure is a flowchart of the preparation raw material step of the present application. DETAILED DESCRIPTION

[0015] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the protection scope of the present application.

[0016] Please refer to Figs. 1-2 The present application provides a technical solution: a preparation process of a cell resuscitation transparent bag, comprising the following steps: First, prepare raw materials: select FEP particles meeting the biological compatibility requirements as the main raw material, and preferentially select medical-grade raw materials with a purity of ≥99.9%; After selecting the raw materials, the FEP particles are placed in a vacuum drying box and dried at 80-100 DEG C and a vacuum degree of ≤-0.09 MPa for 4-6 hours to remove the residual moisture in the raw materials, so as to avoid the generation of bubbles during extrusion and affect the film quality; 3-5 samples are taken from each batch of medical-grade FEP particles for melt index testing (265 DEG C, 5 kg load, index control at 2.0-3.5 g / 10 min) and infrared spectrum analysis to confirm the material consistency and avoid the performance difference of different batches of raw materials affecting the product stability; at the same time, the supplier is required to provide a material analysis report to clearly indicate that the heavy metal content is ≤10 ppm and the low molecular volatile matter is ≤0.1%, so as to ensure that the ISO10993 biological compatibility standard is met; The second step is hot-melt film pressing: the dried FEP granules from the first step are fed into an extruder to melt them. The molten FEP is then extruded into a film through the extruder head. The film is then calendered to adjust its thickness and smooth its surface, resulting in an FEP film with a certain thickness and width. The screw speed of the extruder is adjusted according to the film thickness, usually controlled at 30-50 r / min, with a speed fluctuation range of ≤±2 r / min; at the same time, the back pressure is set to 10-15 MPa to enhance the uniformity of raw material mixing and reduce internal stress of the film; during the extrusion process, the temperature of each zone of the barrel needs to be monitored in real time, and an automatic alarm and adjustment will be triggered when the deviation exceeds ±5℃; The third step is cutting and shaping: the FEP film produced in the second step is cooled down to allow it to cool and solidify, and then a CNC laser cutting machine is used to cut the solidified FEP film. Step 4, heat sealing: Use a pulse heat sealing machine to heat seal the edges of the FEP film cut in step 3 to form the shape of the bag; Before using a pulse heat sealer, the temperature sensor must be calibrated with an error ≤ ±2℃, and the pressure sensor with an error ≤ ±0.02MPa. The heat-sealing head needs to be wiped clean with alcohol wipes and 75% medical alcohol to remove surface residues and prevent contamination of the film during heat sealing. Before each batch of FEP film is produced, 3-5 heat-sealed samples need to be made from the same batch of film. The heat-sealing strength is tested by using a tensile testing machine at a tensile speed of 100 mm / min. The breaking force at the heat-sealed point is required to be ≥15 N, and the breakage location is in the film body rather than the heat-sealed interface. In addition to negative pressure leak testing, the heat-sealed bag must also be visually inspected for heat-sealed edges. Only if there are no bubbles, wrinkles or local unsealed defects can it proceed to the next stage. Step 5, component assembly: Assemble the Luer connector with the FEP bag body processed in step 4 to form a preliminary transparent cell resuscitation bag; Step 6, Sterilization: Finally, the preliminary cell resuscitation transparent bag is placed in a gamma ray sterilizer for sterilization. The sterilized bag is cooled to room temperature (23±2℃) in a Class 10,000 cleanroom and then sealed and packaged to prepare a transparent bag for cell resuscitation.

[0017] Preferably, the first step involves a screening process after drying the FEP particles. The screening process uses a two-stage screening device: a first-stage 100-mesh vibrating screen to remove large particle impurities, and a second-stage magnetic screen to remove metal debris, ensuring that the raw material is free of impurities with a particle size ≥50μm and preventing pinholes and defects in the film.

[0018] We prioritize the use of medical-grade FEP particles with a purity of ≥99.9% and strictly adhere to biocompatibility requirements to eliminate the potential harm to cells from impurities in low-purity raw materials. This ensures that no harmful substances leach out when the transparent bag comes into contact with the cell culture medium, providing a fundamental guarantee for cell viability during the cell resuscitation process.

[0019] The extruder barrel in the hot melt molding process is divided into five temperature zones. The temperature gradient from the feed inlet to the die head is set as follows: 260℃→280℃→300℃→310℃→305℃, so that the FEP particles gradually melt.

[0020] The extruder head adopts a T-type flat die head. The die gap is 50-100μm according to the target film thickness, and the gap deviation is ≤±2μm. The die surface needs to be polished to make the roughness Ra≤0.02μm.

[0021] The extruder extrudes FEP particles and then calenders the extruded material. The calendered film enters the cooling channel and adopts a three-stage cooling: the first stage is 200°C, the second stage is 150°C, and the third stage is 80°C. The cooling wind speed is controlled at 2-3 m / s to ensure that the film is quickly shaped and free of internal stress residue. After cooling and shaping, the FEP film needs to be equilibrated in a constant temperature and humidity environment (temperature 23±2℃, relative humidity 50±5%) for 24 hours to eliminate internal stress. After equilibration, the flatness of the film needs to be checked using a laser flatness meter. If the warpage exceeds 0.5mm / m, it needs to be reprocessed. The cooled film is conveyed to the winding device via traction rollers, and the winding tension is set to 50-80N to avoid film wrinkles.

[0022] The wavelength of the CNC laser cutting machine is 1064nm. The cutting path is set according to the size of the bag, the cutting speed is controlled at 10-15mm / s, and the laser power is adjusted to 30-50W to ensure that the burr height of the cut is ≤0.1mm.

[0023] The heat sealing head of the pulse heat sealing machine is made of polytetrafluoroethylene, with a surface flatness of ≤0.01mm. The heat sealing temperature for 50μm films is 260-270℃, the pressure is 0.3-0.5MPa, and the heat sealing time is 3-5s.

[0024] Preferably, the Luer connector is smoothed before assembly, with a roughness Ra≤0.1μm, to avoid scratching the bag or leaving residual cells, and then pre-sterilized by gamma rays with a sterilization dose of 25-30kGy.

[0025] When assembling the Luer connector with the FEP bag body, the film at the opening of the FEP bag body is heated to a softened state. The heating temperature is 200-220℃ and the heating time is 1-2 seconds. After heating, the Luer connector is inserted, and an axial pressure of 5-8kN is applied by a crimping tool and held for 10-15 seconds to make the connector and the bag body tightly bonded.

[0026] The installation of Luer joints must be carried out in a Class 10,000 cleanroom, ISO 8 level, where the concentration of suspended particles is ≤352,000 particles / m³. The tweezers, crimping pliers, and other tools used must be sterilized by high-pressure steam at 121℃ for 30 minutes, cooled, and then placed in sterile packaging bags for later use to avoid tool contamination.

[0027] After the Luer connector is installed, in addition to torque testing, sterile saline solution should be injected, with the injection volume being 50% of the bag's capacity. Invert the bag for 30 minutes and observe whether there is any leakage at the connection point. At the same time, check the coaxiality of the connector and the bag body, with a deviation of ≤0.2mm, to ensure smooth infusion during subsequent use.

[0028] Working principle: This solution uses medical-grade FEP particles with a purity of ≥99.9%, meeting biocompatibility requirements, eliminating the harm of impurities, and ensuring no harmful substances are leached out. Moisture is removed by vacuum drying at 80-100℃ and a vacuum degree ≤-0.09MPa for 4-6 hours, followed by two-stage screening to remove impurities with a particle size ≥50μm, ensuring the purity of the raw materials and the integrity of the bag. The extruder features a five-stage temperature gradient: 260℃→280℃→300℃→310℃→305℃, which helps prevent raw material degradation. The T-type die head has a die gap of 50-100μm with a deviation of ≤±2μm, resulting in a uniform, smooth film with high light transmittance that does not crack at -196℃.

[0029] Three-stage cooling (200℃→150℃→80℃) + 50-80N winding tension prevents film warping and wrinkling, reducing scrap rate. 1064nm CNC laser cutting, speed 10-15mm / s, power 30-50W, burr ≤0.1mm, precise dimensions. PTFE end cap flatness ≤0.01mm. The Luer connector is pre-smoothed to Ra≤0.1μm, pre-sterilized with 25-30kGy gamma, softened at 200-220℃, and then crimped with 5-8kN for 10-15s, ensuring a firm and leak-free seal. It is then sterilized with 25-30kGy cobalt-60 gamma, incubated in dual-temperature zones for 14 days to achieve sterility, and cooled and packaged in a Class 10,000 cleanroom. In summary, the transparent bags produced by this process exhibit excellent performance, improve cell resuscitation success rates, are easy to operate, have a high yield rate, are suitable for large-scale production, and possess broad medical value and market prospects. This is the characteristic of the preparation process of the transparent bags used for cell resuscitation. The contents not described in detail in this specification are existing technologies known to those skilled in the art.

[0030] Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A process for preparing a transparent bag for cell resuscitation, characterized in that, Includes the following steps: The first step is to prepare raw materials: FEP particles that meet biocompatibility requirements are selected as the main raw materials, with priority given to medical-grade raw materials with a purity of ≥99.9%; After selecting the raw materials, place the FEP particles into a vacuum drying oven and dry them for 4-6 hours at 80-100℃ and a vacuum degree ≤-0.09MPa to remove residual moisture from the raw materials and avoid generating air bubbles during extrusion that could affect the film quality. The second step is hot melt film pressing: the dried FEP granules from the first step are fed into an extruder to melt the FEP granules, and then the molten FEP is extruded into a film through the extruder head. The film is then subjected to thickness adjustment and surface smoothing by a calendering device to produce an FEP film with a certain thickness and width. The third step is cutting and shaping: the FEP film from the second step is cooled down to allow it to cool and solidify, and then a CNC laser cutting machine is used to cut the solidified FEP film. Step 4, heat sealing: Use a pulse heat sealing machine to heat seal the edges of the FEP film cut in step 3 to form the shape of the bag; Step 5, component assembly: Assemble the Luer connector with the FEP bag body processed in step 4 to form a preliminary transparent cell resuscitation bag; Step 6, Sterilization: Finally, the preliminary cell resuscitation transparent bag is placed in a gamma ray sterilizer for sterilization. The sterilized bag is cooled to room temperature (23±2℃) in a Class 10,000 cleanroom and then sealed and packaged to prepare a transparent bag for cell resuscitation.

2. The preparation process of a transparent bag for cell resuscitation according to claim 1, characterized in that: The first step involves a screening process after drying the FEP particles. The screening process uses a two-stage screening device: a 100-mesh vibrating screen to remove large particle impurities and a magnetic screen to remove metal debris, ensuring that the raw material is free of impurities with a particle size ≥50μm and preventing pinholes and defects in the film.

3. The preparation process of a transparent bag for cell resuscitation according to claim 1, characterized in that: The extruder barrel in the hot melt molding process is divided into five temperature zones. The temperature gradient from the feed inlet to the die head is set as follows: 260℃→280℃→300℃→310℃→305℃, so that the FEP particles gradually melt.

4. The preparation process of a transparent bag for cell resuscitation according to claim 1, characterized in that: The extruder head adopts a T-type flat die head. The die gap is 50-100μm according to the target film thickness, and the gap deviation is ≤±2μm. The die surface needs to be polished to make the roughness Ra≤0.02μm.

5. The preparation process of a transparent bag for cell resuscitation according to claim 1, characterized in that: The extruder extrudes FEP particles and then calenders the extruded material. The calendered film enters the cooling channel and adopts a three-stage cooling: the first stage is 200°C, the second stage is 150°C, and the third stage is 80°C. The cooling wind speed is controlled at 2-3 m / s to ensure that the film is quickly shaped and free of internal stress residue. The cooled film is conveyed to the winding device via traction rollers, and the winding tension is set to 50-80N to avoid film wrinkles.

6. The preparation process of a transparent bag for cell resuscitation according to claim 1, characterized in that: The wavelength of the CNC laser cutting machine is 1064nm. The cutting path is set according to the size of the bag, the cutting speed is controlled at 10-15mm / s, and the laser power is adjusted to 30-50W to ensure that the burr height of the cut is ≤0.1mm.

7. The preparation process of a transparent bag for cell resuscitation according to claim 1, characterized in that: The heat sealing head of the pulse heat sealing machine is made of polytetrafluoroethylene, with a surface flatness of ≤0.01mm. The heat sealing temperature for 50μm films is 260-270℃, the pressure is 0.3-0.5MPa, and the heat sealing time is 3-5s.

8. The preparation process of a transparent bag for cell resuscitation according to claim 1, characterized in that: Before assembly, the Luer connector is smoothed with a roughness Ra≤0.1μm to avoid scratching the bag or leaving residual cells. Then it is pre-sterilized by gamma rays with a sterilization dose of 25-30kGy.

9. The preparation process of a transparent bag for cell resuscitation according to claim 1, characterized in that: When assembling the Luer connector with the FEP bag body, the film at the opening of the FEP bag body is heated to a softened state. The heating temperature is 200-220℃ and the heating time is 1-2 seconds. After heating, the Luer connector is inserted, and an axial pressure of 5-8kN is applied by a crimping tool and held for 10-15 seconds to make the connector and the bag body tightly bonded.

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