Patent Application
20250186973
This application claims the priority benefit of Taiwan application serial no. 112148220, filed on Dec. 12, 2023. The entirety of the above-mentioned patent application is hereby incorporated by reference herein and made a part of this specification.
The disclosure relates to a filter material and a manufacturing method thereof, and in particular to a filter material used to remove cells and biomolecules and a manufacturing method thereof.
Filter materials generally used for purification are usually given specific physical properties through chemical surface modification or surface plasma modification. However, the chemical surface modification usually causes the structure of the filter material to be damaged and chemical solvents are likely to remain, which results in poor filtration efficiency and safety concerns. A method of the surface plasma modification usually makes the surface property of the filter material easy to change over time, and as a result, the method has a disadvantage of low stability.
The disclosure provides a filter material and a manufacturing method thereof, which has effects of good filtration efficiency, good safety, and high stability.
A filter material of the disclosure may be used to remove cells and biomolecules. The filter material includes a polymer nonwoven fabric and a modifier. The modifier is fixed on the polymer nonwoven fabric. Critical wetting surface tension of the filter material is between 45 dynes/cm and 115 dynes/cm. A surface electrical property (zeta potential) of the filter material is between −50 mV and +50 mV. There is no chemical solvent residue on the filter material.
In an embodiment of the disclosure, the polymer nonwoven fabric includes ethylene vinyl acetate (EVA), polypropylene (PP), ultra-high molecular weight polyethylene (UHMWPE), polyoxymethylene (POM), polybutylene terephthalate (PBT), polyethylene terephthalate (PET), polyamide (PA), polycyclohexylenedimethylene terephthalate (PCT), polyetheretherketone (PEEK) or combinations thereof.
In an embodiment of the disclosure, the modifier is a cationic surfactant, an anionic surfactant, a zwitterionic surfactant or a nonionic surfactant.
In an embodiment of the disclosure, the modifier has a hydrophobic group and a hydrophilic group connected to each other. The hydrophobic group includes a single long chain containing carbon number 10 to 18, two long chains containing carbon number 10 to 18, or three long chains containing carbon number 10 to 18. The hydrophilic group includes a hydrophilic group with a cation, a hydrophilic group with an anion, a hydrophilic group with a zwitterion, or a hydrophilic group without an ion. Hydrophile-lipophile balance of the modifier is 6 to 18.
In an embodiment of the disclosure, the modifier is hexadecyl-trimethylammonium chloride, sodium coco-sulfate, lauramidopropylamine oxide or polyethylene glycol distearate.
In an embodiment of the disclosure, an average pore diameter of the filter material is between 1 μm and 50 μm, and a fiber diameter of the filter material is between 1 μm and 10 μm.
In an embodiment of the disclosure, a ratio of the average pore diameter to the fiber diameter of the filter material is between 0.1 and 50.
In an embodiment of the disclosure, the filter material is used to remove white blood cells, wherein a white blood cell depletion ratio of the filter material is greater than 99.99%
In an embodiment of the disclosure, the filter material is used to remove albumins, wherein an albumin depletion ratio of the filter material is greater than or equal to 9%.
In an embodiment of the disclosure, a chemical oxygen demand of an extraction solution of the filter material after water extraction is less than 500 ppm.
A manufacturing method of a filter material includes: first, adding a polymer nonwoven fabric, a modifier, and carbon dioxide gas into a container; second, performing a heating reaction on the container and increasing pressure of the container to obtain a supercritical carbon dioxide fluid; next, dissolving the modifier in the supercritical carbon dioxide fluid to fix a dissolved modifier on the polymer nonwoven fabric; and lowering a temperature and the pressure of the container after the heating reaction is over to recycle the supercritical carbon dioxide fluid and obtaining the filter material.
Based on the above, in the filter material and the manufacturing method thereof of an embodiment of the disclosure, since there is no chemical solvent residue on the filter material, the solution filtered by the filter material may not have any concerns about the safety of human health. Since the manufacturing method of the filter material dissolves the modifier by the critical carbon dioxide fluid as a solvent, there are no chemical solvent residue and no concern about the safety of human health in the filter material of this embodiment.
In order to make the above-mentioned features and advantages of the disclosure more obvious and easy to understand, embodiments are given below and described in detail with reference to the accompanying drawings.
A filter material of this embodiment is used to remove cells and biomolecules. The cells may be, for example, white blood cells, and the biomolecules may be, for example, albumins, but are not limited thereto. For example, in response to the filter material of this embodiment used to remove the white blood cells, a white blood cell depletion ratio of the filter material may be, for example, greater than 99.99%, and in response to the filter material of this embodiment used to remove albumins, an albumin depletion ratio of the filter material may be, for example, greater than or equal to 9%, but is not limited thereto.
In this embodiment, critical wetting surface tension (CWST) of the filter material may be, for example, between 45 dyn/cm and 115 dyn/cm, and a surface electrical property (zeta potential) of the filter material may be, for example, between-50 mV and +50 mV, but is not limited thereto. In addition, since there is no chemical solvent residue on the filter material, the solution filtered by the filter material may not have any concerns about the safety of human health.
In this embodiment, an average pore diameter of the filter material may be, for example, between 1 μm and 50 μm, and a fiber diameter (or a fiber width) of the filter material may be, for example, between 1 μm and 10 μm, but is not limited thereto. In addition, in this embodiment, a ratio of the average pore diameter to the fiber diameter of the filter material may be, for example, between 0.1 and 50, but is not limited thereto.
In this embodiment, a chemical oxygen demand (COD) of the extraction solution of the filter material after water extraction may be, for example, less than 500 ppm, less than 450 ppm, less than 400 ppm, or less than 350 ppm, but is not limited thereto. The COD of the extraction solution of the filter material after water extraction is lower, which means that the filter material may have better safety and less concerns about human health.
The filter material of this embodiment may include a polymer nonwoven fabric and a modifier, where the polymer nonwoven fabric may include semi-crystalline polymer, but is not limited thereto. For example, the polymer nonwoven fabric may include ethylene vinyl acetate (EVA), polypropylene (PP), ultra-high molecular weight polyethylene (UHMWPE), polyoxymethylene (POM), polybutylene terephthalate (PBT), polyethylene terephthalate (PET), polyamide (PA), polycyclohexylenedimethylene terephthalate (PCT), polyetheretherketone (PEEK) or combinations thereof, but is not limited thereto.
In this embodiment, the modifier is fixed on the polymer nonwoven fabric. For example, the modifier may be physically attached to the polymer nonwoven fabric in a physical manner which may include van der Waals force or a hydrogen bond. The modifier has a hydrophobic group and a hydrophilic group connected to each other, and the hydrophile-lipophile balance (HLB) of the modifier may be, for example, 6 to 18, but is not limited thereto. Among them, the hydrophobic group may include a single long chain containing carbon number 10 to 18 (C10-C18), two long chains containing carbon number 10 to 18, or three long chains containing carbon number 10 to 18, but is not limited thereto. The hydrophilic group may include a hydrophilic group with a cation, a hydrophilic group with an anion, a hydrophilic group with a zwitterion, or a hydrophilic group without an ion, but is not limited thereto. Specifically, the modifier may be, for example, a cationic surfactant, an anionic surfactant, a zwitterionic surfactant or a nonionic surfactant, but is not limited thereto. For example, the cationic surfactant used as the modifier may be hexadecyl-trimethylammonium chloride or distearyl dimethyl ammonium chloride; the anionic surfactant used as the modifier may be sodium coco-sulfate, dodecylbenzenesulfonic acid, and sodium dodecylpoly(oxyethylene) sulfate or sodium N-cocoyl glycinate; the zwitterionic surfactant used as the modifier may be lauramidopropylamine oxide, cetyl betaine or lauramidopropyl betaine; the nonionic surfactant used as the modifier may be, polyethylene glycol distearate or polyethylene glycol stearate, but is not limited thereto.
In this embodiment, a surface of the filter material is modified through a green process of supercritical fluid technology, so that the filter material may have a specific physical property and be used to purify the cells or the biomolecules. Specifically, a manufacturing method of the filter material may include but may not be limited to the following steps: first, the polymer nonwoven fabric, the modifier, and carbon dioxide gas are added into a container (such as a high-pressure container); second, the container is heated and the pressure of the container is increased to obtain a supercritical carbon dioxide fluid; next, the supercritical carbon dioxide fluid is used to dissolve the modifier, so that the dissolved modifier is fixed on the polymer nonwoven fabric; next, the temperature and the pressure of the container are lowered after the heating reaction is over to recycle the supercritical carbon dioxide fluid, and the filter material is obtained.
In the manufacturing method of the filter material of this embodiment, the modifier may be added in an amount of, for example, 0.1 wt % to 10 wt % based on a total weight of the filter material, but is not limited thereto.
In the manufacturing method of the filter material of this embodiment, the temperature of the heating reaction may be, for example, 60° C. to 150° C., the time of the heating reaction may be, for example, 30 minutes to 5 hours, and the pressure of the container may be, for example, 70 bar to 500 bar, but is not limited thereto.
Compared with the filter materials that generally perform surface modification by the chemical solvents, the manufacturing method of the filter material of this embodiment dissolves the modifier by critical carbon dioxide fluid as a solvent, and as a result, there are no chemical solvent residue and no concern about the safety of human health in the filter material of this embodiment.
Hereinafter, the experimental examples are used to explain in detail that the filter materials and the manufacturing methods of the above embodiments may have the effects of good filtration efficiency, good safety, and high stability. However, the following experimental examples are not intended to limit the disclosure.
First, the polymer nonwoven fabric, the modifier, and the carbon dioxide gas are added into the high-pressure container. Second, the high-pressure container is heated, and the pressure of the high-pressure container is increased to obtain the supercritical carbon dioxide fluid. Next, the supercritical carbon dioxide fluid dissolves the modifier to fix the dissolved modifier on the polymer nonwoven fabric. Next, the temperature and the pressure of the container are lowered after the heating reaction is over to recycle the supercritical carbon dioxide fluid, and the filter materials of Experimental Examples 1 to 12 are obtained. Among them, the material of the polymer nonwoven fabric, the material of the modifier, the amount of the modifier, the temperature of the heating reaction, the pressure of the container, and the time of the heating reaction used in preparation of the filter materials of Examples 1 to 12 are all recorded in Table 1 below.
Comparative Examples 1 to 3 and Experimental Examples 1 to 12 of the filter materials are analyzed as follows: pore diameter analysis, fiber diameter analysis, surface electrical property (zeta potential) analysis, critical wetting surface tension analysis, chemical oxygen demand analysis, and cytotoxicity analysis, white blood cell filtration effect analysis, and albumin filtration effect analysis. Among them, Comparative Example 1 is the polypropylene without surface modification, and Comparative Examples 2 and 3 are commercially available filter materials respectively.
Different batches (batch 1 to batch 6) of the polymer nonwoven fabric (for example, polybutylene terephthalate) are cut into discs with 25 mm and are placed in a pore diameter analyzer (Innova-100N, Poretech Instrument Inc.), galwet (Surface Tension 15.9 dynes/cm) is dropped to wet the surface of the polymer nonwoven fabric, then the surface is slowly pressured with nitrogen, and is measured the changes in pressure and flow rate. Afterwards, the pore diameter and a number proportion of the pore diameter are calculated according to Washburn equation below, and the results are shown in
where D is the pore diameter, γ is the surface tension of the galwet, θ is a contact angle, and P is the gas pressure.
According to the results in
After the surface of the polymer nonwoven fabric (for example, polybutylene terephthalate) is plated with gold (Agar Scientific), the surface of the polymer nonwoven fabric is observed with an electron microscope (JEOL JSM-7600F), and the fiber diameter is measured. Also, the statistical analysis is carried out, and the results are shown in
According to the results in
The surface electrical property (zeta potential) of the filter material is measured by an electrokinetic analyzer (Anton Paar, SURPASS3). Specifically, a mobile phase with 10 mM KCl (pH6.0) pushes a slit of the two filter materials at a pressure of 600-200 mbar. A charge at the slit exit, and hysteresis of a positive ion (K) and a negative ion (Cl−) are analyzed to measure a surface membrane zeta potential of the filter material, and the results are shown in Table 2.
The critical wetting surface tension of the filter material is measured by a sodium hydroxide aqueous solution and a methanol aqueous solution. Specifically, different concentrations of the sodium hydroxide aqueous solutions (or the methanol aqueous solutions) are formulated, and then 10 drops of the defined concentrations of the sodium hydroxide aqueous solutions (or the methanol aqueous solutions) are dropped on the filter material. After 10 minutes, if the filter material has absorbed more than 9 drops of the sodium hydroxide aqueous solutions (or the methanol aqueous solutions), a surface tension value corresponding to the different concentrations of the sodium hydroxide aqueous solutions (or the methanol aqueous solutions) at 25 degrees Celsius is defined as the critical wetting surface tension of the filter material according to Table 3 (or Table 4) below. A surface tension value of water at 25 degrees Celsius is 72 dynes/cm.
According to the results in Table 2, the critical wetting surface tension values of Experimental Examples 1 to 12 are all greater than 72 dynes/cm (that is, the surface tension value of water), which means that Experimental Examples 1 to 12 have hydrophilicity but no hydrophobicity. In addition, the critical wetting surface tension values of Experimental Examples 3, 5, 6, 8, 9, 11, and 12 are all significantly greater than the critical wetting surface tension values of Comparative Examples 1 to 3, which means that Experimental Examples 3, 5, 6, 8, 9, 11, and 12 may have better hydrophilicity and increase a filtration rate.
5 g of the filter material are immersed in a container containing 100 g of pure water. Next, the container is shaken at 100 rpm for 2 hours in an environment of 75° C. to dissolve or extract a dissolved substance in the filter material to obtain an extraction solution. Afterwards, the extraction solution is added to a digestion reagent (HACH, 3-150 mg/L), heated to 120° C., and undergone reaction for 2 hours to perform an analysis with a chemical oxygen demand detector (Rocker, CD 200). The results are shown in Table 2, and the dissolved substance may be the solvent or the modifier, but is not limited thereto.
According to the results in Table 2, the CODs of Experimental Examples 1 to 12 are significantly less than the CODs of Comparative Examples 2 to 3, which means that Experimental Examples 1 to 12 may have better safety and less concerns about human health.
A same number of the cells is added into a cell culture plate. After the cells are attached to the cell culture plate, the cells divided into different groups (Comparative Example 2, Experimental Example 12, a blank group, a negative control group, a positive control group A, and a positive control group B) are add into the cell culture plates corresponding to treatment solutions and undergone reaction for 24 hours. Among them, the treatment solution of Comparative Example 2 is the extraction solution of the filter material of Comparative Example 2 after water extraction, the treatment solution of Experimental Example 12 is the extraction solution of the filter material of Experimental Example 12 after water extraction; no treatment solution is added to the blank group; the treatment solution of the negative control group is water; the treatment solution of the positive control group A is phenol; and the treatment solution of the positive control group B is dimethyl sulfoxide (DMSO). Next, after cell growth (qualitative analysis) is observed with the electron microscope, 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) is added into the cell culture plate to analyze cell viability (quantitative analysis) with the analytic method of MTT, and the results are shown in
According to the results in
According to the results in
Fresh human blood is collected, and the white blood cell content (cell/μL) in the blood is analyzed with a hematology analyzer (BECKMAN DxH 500 HEMATOLOGY ANALYZER). Then, several layers of the filter materials with a basis weight of 100 g/m2 are combined into a filter to remove the blood by gravity. Next, the filtered filter material is observed with the electron microscope, and the results are shown in
where C0 is the white blood cell content (cell/μL) in the blood before filtration, and C1 is the white blood cell content in the blood after filtration (cell/μL).
According to the results in
According to the results in Table 2, the WBCDRs of Experimental Examples 1, 3, 6, 7, 9, 10, and 12 are similar to the WBCDRs of Comparative Examples 2 and 3, which means that the surface-modified Experimental Examples 1 and 1, 3, 6, 7, 9, 10, and 12 are used to remove the cells and have good filtration efficiency.
A human albumin solution (Plasbumin®-20, GRIFOLS Inc.) is prepared, different concentrations of the albumin solutions (1000, 500, 250, 125 μg/mL) with physiological saline are formulated, and the absorbance values of the different concentrations of the albumin solutions are measured by a protein detection reagent (Bio-Rad Protein Assay) to create a graph of a relationship between the absorbance value and the concentration of the albumin solution, and obtain a calibration curve. Next, the filter material is made into the filter (containing 0.3 g of the filter material) to filter 1.5 mL of the albumin solution (600 μg/mL) by gravity. Next, the protein detection reagent is used to measure the concentration of the filtered albumin solution, an albumin depletion ratio (ADR) of the filter material is calculated by the formula below, and the results are shown in Table 2.
where C0 is the albumin concentration before filtration (μg/mL), and C1 is the albumin concentration after filtration (μg/mL).
Next, if the ADR of the filter material of Comparative Example 1 is used as a standard, the following formula may also be used to calculate a ratio between the ADR of the filter material of the Experimental Example and the ADR of the filter material of Comparative Example 1.
where the ADR is the albumin depletion ratio of the filter material of the Experimental Example, and the ADR1 is the albumin depletion ratio of the filter material of Comparative Example 1.
According to the results in Table 2, the ADRs of Experimental Examples 3, 6, 9, and 12 are all significantly greater than the ADRs of Comparative Examples 2 and 3, which means that Experimental Examples 3, 6, 9, and 12 are used to remove the biomolecules and have good filtration efficiency.
After respectively storing the filter materials of Experimental Example 3 (or Experimental Examples 1, 6, 7, 9, 10, and 12) manufactured in the same batch for different periods, analyses of the white blood cell filtration effect and the albumin filtration effect of the filter materials are conducted. The results indicate that the differences in the white blood cell filtration effects (or the albumin filtration effects) measured among different storage times of the filter materials are small. For example, the difference in the WBCDRs measured among different storage times of the filter materials is less than or equal to 0.01% (i.e., the depletion ratios are all ≥99.99%), and the difference in the ADRs measured among different storage times of the filter materials is less than or equal to 5%. This suggests that the surface properties of the filter material in Experimental Example 3 (or Experimental Examples 1, 6, 7, 9, 10, and 12) manufactured in the same batch may consistently exhibit stable characteristics over time.
To sum up, in the filter material and the manufacturing method thereof of an embodiment of the disclosure, since there is no chemical solvent residue on the filter material, the solution filtered by the filter material may have no concern about the safety of human health. The manufacturing method of the filter material dissolves the modifier using critical carbon dioxide fluid as the solvent. Consequently, there is no chemical solvent residue, and there are no concerns about the safety of human health in the filter material of this embodiment. In addition, compared with commercially available filter materials (such as Comparative Examples 2 and 3), the filter material of this embodiment performs the surface modification by the surfactant (that is, the cationic surfactant, the anionic surfactant, the zwitterionic surfactant or the nonionic surfactant), so that the filter material of this embodiment has better hydrophilicity and may increase the filtration rate. Moreover, the filter material of this embodiment has better safety, less concerns about human health, and is used to remove the biomolecules with good filtration efficiency.
It will be apparent to those skilled in the art that various modifications and variations can be made to the disclosed embodiments without departing from the scope or spirit of the disclosure. In view of the foregoing, it is intended that the disclosure covers modifications and variations provided that they fall within the scope of the following claims and their equivalents.
| Number | Date | Country | Kind |
|---|---|---|---|
| 112148220 | Dec 2023 | TW | national |
