Preparation Of Pbt Electrospun/Melt-blown Composite Filtration Materials For Blood Filtration Application

Blood is one of the most important components in human body to keep the body metabolism and life safety. When the blood volume or blood component content is insufficient, human life would be threatened. At this moment, blood supplement should be carried out immediately. As the improvement of medical science, blood transfusion has been deeply studied. By now, the blood transfused to patients mostly comes from the donation of volunteers. Before the blood is transfused to patients from other body, it should be guaranteed that no dangerous cells or virus in blood transmission from other body beside the supervision of bloody types. At present, the studies show that the human leucocyte antigens (HLA) in white blood cells (WBC) of human blood perform the functions of protection, body immunity and the phagocytosis of various viruses. Moreover, the blood viruses (like cytomegalovirus (CMV), Epstein-Barr virus (EBV), human T-cell lymphotropic virus (HTLV), hepatitis B/hepatitis C, and HIV, etc.) are all parasitized in the WBCs of infective body. So if the blood from donation is transfused to patients without reservation, transfusion adverse reactions are easily to happen. Therefore, the removal of WBCs before transfusion is very beneficial to the prevention of those adverse reactions. Now it has been proved that low WBCs concentration blood in transfusion could prevent the happen of non-hemolytic febrile transfusion reactions (FNHTR) of red blood cells (RBC), HLA alloimmunization, transmission of CMV and so on.For those reason, the WBCs should be removed as more as possible before the blood transfusion and the effective RBCs and platelets should be reserved at the same time. The previous studies showed filtration was the most effective method for the remove of WBCs. The most filtration materials are mainly melt-blown nonwovens because their fiber diameter is only around several micrometres. Besides the random and disorderly arrangement of fibers are also good for the sieving and adhesion of WBCs. After the blood filtration with melt-blown filter, the quantity of WBCs in blood could decreased from109/L to105/L～106/L, which could basically satisfy the need of most common patients. However, for some special patients with low immunity (like patients after bone marrow transplantation or organ transplantation, premature infant and so on), transfusion safety is still one of their causes of diseases. Hence, the supply of blood with much lower WBC counts could offer them more safety.In order to achieve a higher filtration efficiency of WBCs, the development of high performance filtration materials is an essential condition. In recent years, electrospinning technology has made rapid development. Nanofibers could be conveniently obtained via electrospinning and their application in filtration field drew great attention of researchers. This paper focused on the manufacture of electrospun filtration materials with high efficiency, and their application in blood filtration was especially studied. The study includes the preparation of electrospinning mats, the composite of electrospun mat and melt-blown nonwovens, the blending electrospinning of RSF and PBT to improve the hydrophilic property of filtration materials, the physical and chemical evaluation of filtration material, the design and manufacture of electrospun blood filter and its filtration performance. The manufacture and application of electrospun and melt-blown composite materials were systematically studied. In general, the main conclusions obtained in this paper included:1. PBT was selected as the raw material to prepare the electrospun nanofibers, which was consistent with the raw material of melt-blown blood filter in market because it has great processability and nice blood compatibility. In the preparation of electrospun/melt-blown composite filtration materials, PBT melt-blown nonwovens were used for the collection of PBT electrspun nanofibers. Before PBT melt-blown nonwovens were used, they were firstly treated with electret. TFA and DCM (1:1mixed) were chosen as the solvents of PBT in electrospinning. The experimental results showed the nanofibers made at the concentration of14wt%had uniform surface without breads, and their diameter was relatively small. So14wt%was considered as the optimal concentration in the eletrospinning process. After the surface electret treatment of PBT melt-blown nonwovens, high density of negative charges were formed on their surface. The test results showed the electret treatment was beneficial to obtained finer nanofibers and uniformity of fiber diameters if the electrospinning parameters keep constant. By the orthogonal experimental design of electret parameters, the conclusion was achieved that the melt-blown materials had the biggest surface voltage when the electret voltage, treatment time and treatment distance were60kV,40s and8cm separately. Moreover, the electrospun nanofibers collected with the melt-blown material obtained under these conditions had the finest diameter with smallest standard deviation.2. In order to obtain electrospun/melt-blown composite filtration materials with excellent filtration performance, electrospinning concentration, solution volume and the type of melt-blown used were considered as the key impacting indicators according to the filtration mechanism analysis of fiber filters. Sodium flame filtration efficiency was set as the measurement index to study the orthogonal experiments. Known from range analysis, though the adding of electrospun layer could all improve the filtration efficiency, the selection of electrospinning concentration as low as possible in the stable spinning concentration range was good for the achievement of higher filtration efficiency. Though thicker electrospun layer in composite materials could have higher filtration efficiency, the filtration resistance and quality factor decreased at the same time. Therefore, the selection of electrospun layer should be treated according to the requirement of practical application. Among the above three impacting indicators, the influence of solution volume (relative to the thickness of electrospun layer) to the end filtration efficiency was the largest. After the electrospun/melt-blown composite materials were manufactured to blood filter, their blood filtration efficiency were evaluated. The white blood cells after filtration was only4.88±2.34X104/L, which was only1%-10%of that filtered with traditional melt-blown blood filters. However, the recovery rate of red blood cells decreased at the same time. The filtration time extended greatly from2.47min to65.48min. On one hand, this was caused for the densification of elctrospun layer, on the other side, the electrospun layer was hydrophobic. The wetting and spreading time of blood on filtration materials were much longer. Therefore, the eletrospun/melt-blown materials should be hydrophilic modification to further reduce the filtration time.3. Based on the above research, regenerated silk fibroin (RSF) was blended in eletrospinning of PBT to improve the hydrophilic property of PBT electrospun/melt-blown composite materials. The experiment showed that RSF could also dissolved in TFA/DCM, so there was no need for the adding of new solvents.16wt%was the optimal concentration for the pure electrospinng of RSF according to the study.16wt%RSF and14wt%PBT solutions were mixed for the preparation of blended electrospinng. Blended elcetrospun mats at five blending ratios were evaluated. It was considered that there was no new substance formed in the blended eletrospinning according to the FTIR tests. Besides the diameter of blended electrospun fibers were all smaller than PBT electrospun fibers when the electrospinning process parameters were constant. When the content of RSF was higher than50%, the hydrophilic property and wettability became nice especially when the RSF content was higher than80%. The adding of RSF improve the hydrophilic property of PBT electrospun fibers from aspects like addition of hydrophilic groups, decrease of degree of crystallinity, increase of surface roughness and so on.4. In order to improve the stable of RSF in PBT/RSF blended electrospinning mats, methanol treatment was adopted to decrease the dissolve-loss ratio. The experiments showed molecular conformation of RSF have the changing trend from random coil and α-helix structures to β-sheets after the treatment of methanol. After10min treatment with methanol, the dissolve-loss ratio of blended electrospun mats at37℃for5h was less than5%. As the temperature in practical use was lower than37℃and the using time was shorter than1h, so it was believed that the dissolve-loss ratio in practical use would much less than5%. Beside the change of dissolve-loss ratio, the methanol treatment led to a small decrease of pore size because of the swelling phenomenon. It should be notable that the instant contact angle and wetting time of materials treated with methanol was nicer compared with that without treatment. This was because the treatment made the arrangement of RSF tighter. Therefore, the water drop would connect with more relative hydrophilic groups instantly. In addition, the surface roughness of fibers increased after treatment was another reason for the decrease of contact angle.5. The safety of PBT/RSF blended electrospun mats used as blood filtration materials were evaluated according to the national standard test items like chromatography mass spectrometry, pH value and ultraviolet absorbency at250-320nm of material lixivium, hemolysis ratio and so on. In chromatography mass spectrometry test, no characteristic ion of DCM was found for the blended electrospun fibers. While there was TFA remaining in electrospun fibers. However, after the methanol treatment and vacuum drying, TFA was further removed for nearly90%. The test of fiber mat lixiviums showed that the difference between pH values of lixiviums (made with samples after methanol treatment and vacuum drying) with that of blank control liquid was smaller than1.5, which was the largest limit of national standard requirement. The ultraviolet absorbency at specific wavelength range was also smaller than0.3(largest limit of national standard requirement). However, the lixivium test of electrosping without treatment and drying could not reach the requirement of national standard. Known from the hemolysis ratio test, the hemolysis ratios of all blending ratio electrospun mats in the research were lower than5%required by national standard. This meant the adding of RSF could not lead to the damage of RBCs. Moreover, after the methanol treatment and vacuum drying, the residual solvents could not threaten the RBCs. They could satisfy the requirements of national standard.6. PBT/RSF electrospun mat and PBT melt-blown nonwovens were adopted to manufacture blood filter. And their filtration performance were tested. Known from tests, the WBCs quantity after filtration using these filters were all around104/L, which was much lower than1X106/L (the limit of national standard). The blending of RSF in PBT electrospinning reduced the filtration time of100mL blood from70.56min to38.77min. Though filtration time was still much longer than that of melt-blown blood filter, it was acceptable consideration the great filtration efficiency. Especially for the special patients with low immunity, the removal effect of WBCs was more important. Furthermore, the research also discussed the thickness influence of electrospun layer and melt-blown layer to filtration efficiency. The increase of electrospun layer thickness could obtained nicer filtration effect of WBCs, but it also make it difficult for the pass of RBCs especially when the thickness of electrospun layer was larger than1.48mm. At that time, the RBCs recovery was only78.4%, which was lower than85%required by national standard. Besides, the increasing of electrospun layer thickness also led to the obviously increasing of filtration time. In addition, the experimental results showed reduction of melt-blown layer and filter diameter appropriately could decrease the wastage rate of blood during filtration and obtained well filtration efficiency at the same time, which was significant in the practical application.