Development Of Membrane Adsorbers And Their Application In Blood Purification

Blood purification is an important clinical approach for familial hypercholesterolemia,sepsis,liver and kidney failure related diseases,while the performance,physical and chemical properties of adsorbents play a vital role in blood purification.Currently,commercial adsorbents have problems such as low adsorption efficiency and high cost.In this thesis,a microporous membrane had been used to design membrane adsorbers with different adsorption characteristics through chemical modification.The adsorption performance of related adsorption membranes to bilirubin and autoantibodies(the main component is hIgG)had been studied to provide new ideas for blood purification research.Firstly,the microporous walled micro-capillary film(MMCF)made of polyvinyl vinyl alcohol(EVOH)had been analyzed.The results of static contact angle and hemolysis test had showed that the MMCF membrane had good hydrophilicity and blood compatibility,which was suitable to be used as matrices.The pore size and pore size distribution of MMCF membranes and agarose microsphere adsorbents had been analyzed by scanning electron microscopy,mercury injection and inverse size exclusion methods.MMCF had a pore size range of 100-10000 nm,and the channel size was 300 ?m,while the latter had an average pore size of 100 nm and pore size distribution of 2-240 nm.A MMCF column had been further assembled to measure the column pressure at different flow rates and to verify its resistance to high flow rates.The non-specific adsorption of the MMCF membrane adsorption column had been analyzed using two major proteins in human blood(hIgG and HSA)as model proteins,and the results showed that the non-specific adsorption of the membrane was extremely low,which was good for blood adsorption applications.Ligands including ethanolamine(ETA),ethylenediamine(EDA),diethylenetriamine(DETA),diethylamine ethyl(DEAE)and hexamethylenediamine(HMD)had been chemically bonded on the MMCF membrane to prepare a series of MMCF membrane adsorbers for bilirubin adsorption.It had been found that the static adsorption capacity of the HMD-MMCF membrane was 13.5 mg/g matrix,and when the bilirubin concentration was 0.25 mg/ml,the adsorption equilibrium was reached and the saturated adsorption capacity was 28.4 mg/g matrix.In addition,the adsorption performance of HMD-MMCF membrane was affected by NaCl and albumin additives.Compared with the unmodified MMCF column,the dynamic adsorption efficiency of the HMD-MMCF column was better.In addition to remove bilirubin,the HMD-MMCF membrane had been further coupled with a tetrapeptide ligand Ac-FYHE to specifically remove excess autoantibodies from patients with autoimmune diseases.The experimental results of infrared spectrum and scanning electron microscope showed that the MMCF was successfully modified and the microstructure was not changed.Different concentrations of hIgG solutions had been used to investigate the performance of the Ac-FYHE-MMCF membrane adsorbers,and the static equilibrium capacity and dynamic equilibrium capacity were 9.31 mg/ml and 3.47 mg/ml,respectively.By changing the flow rate during protein adsorption,it had been found that the Ac-FYHE-MMCF column had slight decrease of hIgG capture rate,and it still maintained a good adsorption capacity at high flow rates.hIgG had been separated from hIgG/HSA mixtures and human serum at pH 7.4,and the purity was both over 80%,which indicates that the Ac-FYHE-MMCF membrane adsorder has good selectivity and high processing efficiency.