Ultrafiltration is a form of membrane filtration in which hydrostatic pressure forces a liquid against a semipermeable membrane. Suspended solids and solutes of high molcular weight are retained, while water and low molecular weight solutes pass through the membrane. Ultrafiltration is typcially characterized by a membrane pore size between 1 and 1000 kDa and operating pressures between 0.101 and 10 bar. Membranes are characterized by their nominal molecular weight limit (NMWL) also referred to as their molecular weight cut-off (MWCO). This represents their ability to retain molecules larger than those of a given size. An ultrafiltration membrane’s MWCO or NMWL is expressed in kilodaltons and abbreviated as K (i.e., 10k, 30, etc).

Different types of UF membranes are commercially available made of ceramic, semi-conducting or polymeric materials, etc (WO 2009/139624). 

Ultrafiltration can be performed with tangential flow filtration (TFF mode) (US 2006/0051347). Ultrafiltration is normally carried out in TFF mode, in which fluid passes across the filer, tangential to the plane of the filter surface. (Liu, “Recovery and purification process development for monoclonal antibody production” mAbs,  2:5: 480-499 (2010)  See TFF right hand column. 

Selection of UF

UF membrane selection is based on several parameters such as the following:

(1) separation performance (retention): The most critical paramter here is determiend by NMWL (normal molecular weight limit). Membranes are available in numerous NMWLs.

(2) processing rate (flux): Membrane flux, as measured by flow rate per unit area determines how much membrane is required to process the feed stream in the desired time period. Higher flux results when the actual pore size closely resembers the desired NMLWL cut off. Maximizing membrane pore size allows process fluids to pass more quickly, thus increasing flux.

(3) Mechanical integrity: a Strong mechanically intact membrane will perform consistently for a long period of time.

Particular Schemes with UF (as to antibody purification using UF see antibody section)

Cordle (EP0363896A2) discloses an ultrafiltration process for enriching and concentrating a desired protein from a fluid by using metallic oxide ultrafiltration membranes and a pH shift. The process uses the same ultrafiltration membrane for two successive ultrafiltrations, shifting the pH between the two successive ultrafiltrations, in order to remove materials of lower molecular weight or higher molecular weight than the desired protein on the basis of charge as well as size. The process makes feasible the fractionation of immunoglobulins such as IgG and involves two factors; 1) the metallic membrane produces a high rejection of IgG at a pH of 5.8 or lower but a much lower rejection of IgG at a pH of 6.5 or greater and 2) the metallic membrane allows continual passage of smaller MW proteins at any pH level. In one embodment, a fluid is exposed to a first metallic oxide UF membrane at a pH which is below the isoelectric point of a slected protein whereby a retentate containing the protein is produced, then subjecting the retentate to a second UF at a pH above the isoelectric point of the protein whereby a permeate containing the selected protein is produced. 

Pre-filtration (reduces aggregation of the UF)

–Activated carbon filters:

Martin (EP1577319A1) teaches a prefilter positioned upstream of other purification systmes such as affinity chromatography and UF which is used to reduce the presence of non-specific binding (NSB) species that enter the system. Suitable agents for the prefilter include activated carbon, fumed slica, glass etc.

–Depth Filters:

Siwak (US2003/0201229; see also US7,118,675) discloses selectively removing plugging constitutions  from a biomolecule containing solution in a normal flow (NFF) filtration process before vrial filtration using UF. In the first step one or more layers of adsorptive depth filters are used to remove plugging constituents in a normal flow filtration mode of operation. The plugging constituent free stream can then be filed through one or more UF membranes to retain virus particles and allow passage of a plugging constituent free biomol;ecule.

–Negatively charged medium:

Kazlov (US2013/0056415) discloses using a negatively charged microporous filtraiton meidum for use as prefiltration membranes for slectively removing protein aggregates form a protein solution