Liquid phase separation
Electrocoagulation
Membrane distillation
MD is a thermally driven separation process, in which only vapor molecules are able to pass through a porous hydrophobic membrane. This separation process is driven by a vapor pressure gradient across a porous hydrophobic membrane. Direct contact membrane distillation (DCMD) is the most commonly used configuration of MD. In DCMD, hot feed water and cold distilled water flow on opposite sides of a hydrophobic membrane. The membrane acts as a thermal insulator as well as a physical barrier between the hot feed and the cold distillate. Water vaporizes from the hot feed, passes through the membrane pores and condenses on the distillate side. MD can provide variety of advantages when treating high salinity produced waters, including: near complete rejection of dissolved and suspended species, lower operating pressures than pressure-driven separation processes (such as RO), lower operating temperatures compared to thermal distillation and the possibility of using waste-heat as the energy source for the process. Since it is mostly the water vapor that crosses the membrane, dissolved solids remain in the concentrated retentate and high quality permeate is recovered.
Forward osmosis
Forward osmosis, the osmotic pressure-driven spontaneous transport of solvent molecules across the semi-permeable membrane, has been extensively used in the treatment of wastewater, brackish water; concentration of digested biomass and other bioactive materials from food byproducts; direct potable use of advanced life support system; hydration bags, osmotic pumping for drug delivery, power generation, desalination and membrane bioreactors [1–6]. Since forward osmosis is operated at low or almost no hydraulic pressure; a high rejection of components can be achieved without significant irreversible fouling. The low energy inputs lead to a low-cost operation. Furthermore, due to mild operation conditions, physical properties like color, taste, aroma, nutrition, etc. were found to retain in the products. This is mainly important in food and biomedical applications. Several reports are available in the literature overviewing the principle, applications, recent development, and future prospects on forward osmosis-based membrane separation processes.
Magnetically responsive membrane
These magnetic field-responsive membranes are unique for a number of reasons. Chemical modification of the membrane surface imparts fouling resistance. The movement of the magnetically responsive nano-brushes leads to mixing at a low Reynolds number at the membrane surface. Thus a hydrodynamic method is used to disrupt concentration polarization. Previous experimental and theoretical studies show that mixing of the feed near the membrane surface improves mass transfer by disrupting concentration polarization and reducing the rate of cake formation. By growing a magnetically responsive nanolayer from the membrane surface mixing is induced at the membrane fluid interface thus maximizing the disruption of the concentration polarization boundary layer. Unlike many previous studies that depend on changes in the bulk feed (e.g. pH, temperature) to change the conformation of the responsive groups present, no such change is required as the grafted polymer brushes respond to an oscillating magnetic field
Zwitterionic material system
Fouling mitigation is a major issue for most membrane separation applications. For membranologists, the main solution to mitigate the fouling deposited on the membrane is to modify the membrane properties or structure. Throughout the history of developing antifouling materials, they could be divided into three generations, 2-hydroxyethyl methacrylate (HEMA)-based, PEGylated-based, and zwitterionic-based materials. HEMA-based material has rich -OH moieties to generate a tight hydration layer reducing the hydrophobic foulant approach to the layer, but their antifouling property may be lost once it contacts with complex media like human blood serum and plasma. The complex physicochemical interactions between the protein and the surface can affect their fouling behavior as well. The second generation is a PEG-based or oligo (ethylene glycol) (OEG) material and it demonstrated an excellent behavior to avoid protein and cell adhesion onto the interface owing to the close hydration layer around OEG chain. Both HEMA and PEG materials have shown a mediocre antifouling performance once the positively charged foulants are in contact though a good fouling resistance to the negatively charged pollute because of an electrostatic repulsion. Thus, zwitterionic-based material has gradually attracted researcher’s attention, and therefore regraded as third-generation antifouling material. Zwitterionic materials are promising candidates to enhance surface hydrophilicity and augment both antifouling and antibacterial properties of the membrane because it could create a strong hydration layer through electrostatic and hydrogen bond interaction. The typical zwitterionic material systems can be separated into phosphobetaine methacrylate (PBMA), sulfobetaine methacrylate (SBMA), and carboxybetaine methacry-late (CBMA). Similarly, they are comprised of cations and anions on the same side chain, which could prevent surface adhesion by either positive or negatively charged foulants. The zwitterionic phoshatidycholine displays anti-biofouling ability and biocompatibility to protect cell membranes, consequently, it could theoretically be used its concept to fabricate or design a related antifouling membrane or interfaces.
Catalysis membrane
Waste disposal continues to be a major social and economic problem. As rapid urbanization and population growth pressures the manufacturing and agricultural industries to keep up with demand, waste generation will accelerate. Biomass waste, such as agricultural residues or food waste, is an underutilized feedstock for the synthesis of valuable products. This technology has two components, a unique catalyst to hydrolyze cellulosic biomass into fermentable sugars/chemical intermediates and a porous membrane for separating the hydrolyzed products. Our enzyme-mimic catalyst is a polymeric nanostructure synthesized and immobilized on a porous membrane substrate to depolymerize polysaccharides including cellulose and hemicelluloses from lignocellulosic biomass to soluble sugars and chemical intermediates. This catalyst consists of two adjacent polymer nanostructures, a polystyrene sulfonic acid (PSSA) and poly (ionic liquid) (PIL) chains grafted from a membrane support. PSSA and PIL chains will act cooperatively to bind and hydrolyze the biomass substrate, similar in nature to the functions of cellulase enzymes. The acidity and catalytic activity/selectivity of our designed catalyst can be tuned and optimized by ring substitution and by varying independently the chain length/chain density of the nanostructures. A porous membrane with an appropriate pore size will enable the separation of the monomer sugars/chemical intermediates immediately after they are released, thus improving the overall yield and selectivity.
Pharmaceutical application
Virus filtration
Virus filtration involves costly, single-use virus filters to ensure the safety of therapeutic proteins. Adventitious virus contamination is a critical issue in the manufacture of therapeutic proteins such as monoclonal antibodies (mAbs), Fc fusion proteins, insulin, etc. Virus filters are both essential and obligatory devices for ensuring high purity biopharmaceutical products. The predominant mechanism of virus filters is size-exclusion via membrane rejection of viruses. The virus filter dimensions ensure that mAbs can pass through due to their small hydrodynamic diameters (10 nm). Conversely, parvoviruses used as model viruses are rejected by the virus filter membrane due to their diameter (18-26 nm). To pass through a BioEX membrane, a mAb passes multiple, tortuous voids and 20 nm sized capillaries in series. Viruses are therefore captured by virus filters while mAbs flow through. Virus filtration uses porous polymeric membranes in normal flow mode. A useful metric of successful virus filtration is to attain four logs (orders of magnitude) reduction in virus titer of product. Three main indices are used to benchmark virus filters’ performance, and they include: log reduction values of viruses, achievable throughput, and protein recovery. Virus filter productivity is hampered by fouling, and we seek to exhaustively research mitigation of fouling. Without prefiltration, highly polished mAbs can still foul virus filters aggressively. Conversely, prefiltered mAbs show improved flux and reduced fouling of downstream virus filters. There are different prefilters, including cation exchange (CIEX) prefilters, anion exchange (AIEX) prefilters, HIC prefilters and multimodal prefilters. Scientific opinions suggest that principal foulants of virus filters are analogs of the mAb since virus filtration occurs towards the end of downstream processing where trace amounts of non-mAb impurities subsist. Prefilter selection criteria have been mostly empirical, and the need arises for rigorous research into prefilter best practices. Prefilters can adsorb mAb aggregates, mAb charge variants, misfolded mAbs, and molecular weight variants.
Ion exchange membrane chromatography(IEX)
IEX prefiltration removes mAb species with different charge and size. Ion exchange chromatography separates biomolecules based on their net and surface charge distribution. Cation exchange (IEX-S) membranes or resins are materials with the attribute of displaying permanent negative charged ligands on the surface. Anion exchange (IEX-Q) membranes or resins are materials with the attribute of displaying permanent positive charged ligands on the surface, which can then be used to partition anionic species from a sample. Charge heterogeneity of proteins is a useful partitioning parameter for anion and cation exchange membranes or resins. Cation exchange chromatography is the reversible adsorption of cations to a cation exchange membrane or resin. Anion exchange chromatography is the reversible adsorption of anions to an anion exchange membrane or resin. Partitioning of bio-analytes occurs by selective adsorption based on the mAb surface charges at prevailing pH and ionic strength. Ion exchange prefilters perform well for therapeutic proteins in low ionic strength buffer formulations.
Hydrophobic interaction chromatography(HIC)
HIC prefiltration removes mAb species with different hydrophobicity from the remaining mAb species. These differences dictate molecular interactions with ligands on the HIC prefilter. HIC prefilters typically have phenyl ligands. Hydrophobic interaction prefilters require a high salt concentration buffer. High ionic strength buffers reduce a protein’s solvation layer, enabling exposed hydrophobic patches to adsorb on the HIC ligands. Hydrophobic patches on the proteins’ surface are critical in HIC prefiltration. Hydrophobic interaction enables the separation of proteins under native, non-denaturing conditions such as ambient temperature and physiological pH.
Bioreactor harvesting
Bioreactor harvesting is the first of the downstream purification operations in the manufacture of biopharmaceuticals. The product of interest, typically a protein-based therapeutic, is separated from the particulate matter in the bioreactor: the cells and cell debris. The harvesting method of choice depends on the type of cells, mode of bioreactor operation, scale of manufacturing, and product properties. Typical unit operations include centrifugation, expanded bed chromatography, depth filtration, and tangential flow filtration (TFF). Several investigations have examined the use of alternating tangential flow filtration (ATF) to minimize fouling (by periodically reversing the direction of the feed flow into the module). Still, membrane fouling remains a major challenge. Membrane fouling is very complex and is affected by the hydrophobicity, charge, and polarity of the foulants and the properties of the membrane as well as the operating conditions. Our group proposed several fouling analysis methods quantitatively and qualitatively, including mathematics model, confocal microscopy, and foulant identification. The model contains three fitted parameters which can easily be determined from preliminary experiments. The model can be used to estimate the capacity of the filter for a given feed stream. The confocal microscopy shows the location of entrapment of particulate matter on and within the membrane. Foulant identification refers to extraction of foulants, separation by SDS-PAGE, followed by mass spectrum identification. The identification can give the name of the foulants, and its relative ratio.
Computation simulation