Membrane Filter Characteristics

Anisotropic Membrane: A membrane in which the pore openings are larger on one side than the other.

Bubblepoint Test: A test to determine the integrity and pore sixe of a filter. The differential pressure at which a steady stream of gas bubbles is emitted from a wetted filter under specific test conditions. The bubble point test measures the largest pore.

Depth Filter: A matrix of randomly distributed filters or particles creating a tortuous path of nominally rated size.

Differential Pressure: The difference in pressure between the upstream and downstream sides of the filter.

Diffusion Test: A test to determine the integrity of a filter. The test is based upon the transition from diffusional flow to bulk flow, of a gas, through a wetted filter. Either the gas or the downstream liquid, displaced by the gas, may be measured.

Downstream Side (of filter): The filtrate side of the filter.

Filter (noun): A device for carrying out filtration which consists of the filter medium and a suitable holder for constraining and supporting it in the fluid path.

Filter (verb): To pass a fluid containing particles through a filter medium whereby particles are removed from the fluid.

Filter Medium: The permeable material that removed particles from a fluid being filtered.

Filtrate: The fluid which has passed through a filter.

Filtration: The process by which particles are removed from a fluid by passing the fluid through a permeable material.

Flow Rate: Determines the volume of liquid which will flow through the filter at a fixed pressure and temperature.

Hydrophilic: Refers to a filters ability to naturally wet with water. “Water-loving” filter.

Hydrophobic: Refers to a filters lack of ability wet with water. “Water-hating” filter. Ideal for venting applications.

Integrity Test: A non-destructive test which is used to predict the functional performance of a filter. The valid use of this test requires that it be correlated to a standardized bacterial retention test. Examples: Bubblepoint test, Diffusion Test, Flow Rate Test.

Isotropic Membrane: A membrane in which the pore openings are the same diameter on both sides of the membrane.

Membrane Filter: A continuous polymeric matrix with channels of defined size.

Non-Fiber Releasing Filter: A filter which after any appropriate pretreatment, such as washing or flushing, will not release fibers into the filtrate of the product that is being filtered.

Particle: A discernible mass having an observable length, width, thickness, including particulates and bacteria.

Pore Size (absolute): The pore size at which a particle of defined size will be retained with 100% efficiency under specified test conditions, ie., a .02µm sterilizing filter will retain 10 organisms per cm² of Pseudomonus diminuta at 30 psig and ambient temperature.

Pore Size (nominal): The pore size at which a particle of defined size will be retained with an efficiency below 100% (typically 90-98%). Rating methods differ widely between manufacturers.

Pore Size Rating: The maximum diameter of a channel through the filter medium.

Porosity: The percentage of the filter area which is porous.

Sterilizing Filter: A non-fiber releasing filter which produces an effluent in which no microorganisms are demonstrable when tested by the method specified in the current edition of the United States Pharmacopeia.

Throughput: Describes the dirt handling capacity. That is, how long the liquid will continue to flow through the membrane before the membrane clogs. The lower the flow rate and throughput, the longer it takes the researcher to complete an analysis. Quality control during the manufacturing process monitors and determines a membrane’s bubblepoint, flow rate and throughput.

Upstream Side (of filter): The feed side of the filter.

Membrane Filter Specifications

Adsorption: Retention of gas, liquid, solid or a dissolved substance on a surface due to positive interaction (attraction) between the surface and the molecules of the adsorbed material. The interactive forces can be electrostatic (coulombic) or non-electrostatic (dipole-dipole and hydrophobic). Adsorption to a membrane or filter device can occur in a specific manner (affinity) or non-specifically.

Autoclave(ing): chamber for sterilizing filters or equipment with saturated steam by using constant high temperature and pressure (commonly 121ºC, 15 psi). Many materials requiring sterilization (such as cell culture media and injectable drugs) are degraded by the heat of an autoclave and must be sterilized by other means such as filtration.

Binding Constant: Defined as the concentration of a ligand that saturates the binding of half of the available binding sites. It is a combination of the available target (receptor) and the affinity of the lignad. Also known as the dissociation constant Kd.

Biological Safety Test is a general term used to categorize tests performed to determine whether the filter’s materials of construction are capable of including measurable degrees of systemic toxicity, localized in ski irritation, sensitization reaction, or other biological responses. Either in vivo or in vitro test methods may be employed. Tests like the “United States Pharmacopoeia (USP) Biological Reactivity Test, In Vivo <88>” ensure that the filters can be exposed to the test solutions without causing an adverse reaction.

Bubble Point: The air pressure required to force liquid from the largest wetted pore of a membrane. It serves as an indication of pore size and rates the filter’s ability to serve as a particle barrier. The bubble point is dependent on the liquid used to wet the membrane. For a given pore size, the bubble point will be higher in a liquid with a higher surface tension (such as water) than in a liquid with a lower surface tension (such as isopropyl alcohol). The bubble point rating is determined when the largest pore yields a bubble; the larger pore, the less pressure required to form a bubble. Expressed in units of pounds per square inch (psi) or bar for membranes.

Coefficient of Variation (CV): measure of the variation that can occur between samples during a binding assay. Variation can result from liquid transfer, non-specific binding, improper washing, and anomalies with the plate. Studies indicate that the AcroWell plate has low CVs making it useful for binding assays.

Counts per Second (CPS): Relates to the number of photons detected that are given off by the scintillant counter (radioactivity) or multilabel counter (fluorescent).

Cytotoxicity Test: test designed to determine the biological reactivity of mammalian cell cultures following contact with the plastic or membrane with specific extracts prepared from the material under test. The procedure allows for extraction of the material at physiological to non-physiological temperatures for varying intervals.

Differential Pressure: Differential Pressure (ΔP) is the difference between the pressure in the system before the fluid reaches the filter (upstream pressure) and the system pressure after the fluid flows through the filter (downstream pressure) in a constant flow situation. As the filter begins to clog, differential pressure increases.

DOP Test: A measure of the efficiency of a filter for the removal of particulate from air, based on retention of 0.3 µm Dioctyl Phthalate (DOP) aerosol droplets, usually expressed as a percentage. A High Efficiency Particulate Air (HEPA) filter must retain at least 99.97% of 0.3 µm DOP droplets. The 0.3 µm size was chosen because particles of this size are the most difficult to retain in many air filters.

Effective Filtration Area (EFA): EFA is the filter area that is available for filtration. For a given membrane, the larger the filter area, the higher the flow rate at a given initial differential pressure. Filter media and devices are available in a wide range of sizes with different EFAs.

Endotoxin: complex molecule (lipopolysaccharide) which forms an integral part of a gram of negative bacterial cell walls and is released when the integrity of the wall is disturbed, i.e., cell division, growth, and death. Endotoxins may be released during biosynthesis of a recombinant DNA product, thus necessitating purification steps to ensure their removal.

Extractables: Substances present in the composition of the filter media or the filter manufacturing process that may be leached into the fluid as it is filtered, thereby affecting its purity. Extractables may include manufacturing debris, surfactants, and adhesives. The type and amount of extractables will vary with the type of liquid being filtered. Extractable components which can end up as contaminants may be minimized with sufficient preflushing.

Filter Efficiency: Measurement of the percentage of particles which are removed from the fluid by the filter. In filtration of liquids, filter efficiency is given on the basis of particles at or above a certain diameter in size. In gas filtration, efficiency is stated as including all particles, including those at the most penetrating particle size. See the DOP Test for a test of efficiency in air filtration. Some filter manufacturers will report efficiency in terms of the percentage removal of the particles by weight, which does not reveal the number of particles what may pass through the filter. This is a type of nominal filter rating. For high-efficiency filters, this is often replaced by a beta rating. Efficiency can be calculated from a beta value as follows: % Efficiency = (B-1/B) x 100

Filter Life: Ameasure of how long a filter will last before requiring replacement or cleaning. It can be stated either in terms of time (e.g., 30 days between changes) or volume of fluid filtered (e.g., 10,000 liters processed between filter changes). A filter’s actual life will depend on what particulates and conditions it is exposed to in actual usage, so filter life ratings from lab testing with standard contaminants can be used for comparison, but do not necessarily predict actual service life. To predict actual life, testing with the application fluid under actual operating conditions is required. Typically, the useful life of a filter can be determined by a two-to-four fold increase of differential pressure in a constant flow system or a drop in flow rate of 50 to 80% in a constant pressure system.

Fluorescence: Light emitted from fluorophore (fluorescent molecule) as a result of excitation. The excitation wavelength (color) is different than the emission wavelength. The difference between these wavelengths is known as the strokes shift. The emitted light is detected in a specialized detector such as the Victor multi-label counter. Most fluorophores give a sample emission that is about 1 picosecond after excitation while in time-resolved fluorescence the emission occurs after a microsecond lag.

Good Manufacturing Practices (GMPs): Regulations promulgated by the Food and Drug Administration governing the manufacture of drugs (Ref. Code of Federal Regulation 21 CFR 210 and 211), medical devices (21 CFR 820), and Large Volume Parenterals (21 CFR 212 proposed). cGMP are the current accepted standards of operation in a regulated industry.

Hold-up Volume: Volume of fluid retained in a filter and/or housing after purging the assembly with air or suitable gas. Hold-up volume is usually considered to be lost volume.

Integrity Test: test to ensure that a sterilizing-grade filter is intact and will function as intended. Recommended integrity tests are the Forward Flow test, Bubble Point test and the Pressure Hold test. Integrity tests on sterilizing-grade filters are correlated with bacterial challenge data.

Limulus Amoeboctye Lysate (LAL) Test: An LAL gel clot test prescribed by the United States Pharmacopeia (USP) to detect and determine the level of bacterial Endotoxins in a substance. The reagent is made from the circulating blood cells (amoeboctyes) f limulus polyphemus, the horseshoe crab.

Luminescence: The emission and detection of light produced by chemical reactions or bioluminescence due directly to the enzyme light production. These enzymes can be used as labels to trace a molecule of interest. It does not require laser extraction like fluorescence because it is a result of a chemical reaction. Luminescence reactions can be carried out on membranes (blots), in a plate, or in a solution. If the reaction is being done in a 96-well form, the use of a white plate enhances the recovery of photons.

Molecular Weight Cut-off (MWCO): Normal rating system for ultrafiltration and nanofiltration membranes. MWCO is defined as the molecular weight of solute of which the membrane retains 90%. Often defined by the molecular weight of dextran particles retained.

Operating Limits: Minimum and maximum parameters set for validation and processing pressures and temperatures.

Permeability: The degree to which a fluid will pass through a permeable substance under specified conditions. The space or void volume between molecules allowing fluid flow.

pH: The pH value of an aqueous solution is a number describing the acidity or alkalinity. A pH is the negative logarithm (base 10) of the concentration of hydrogen ions (equivalents per liter). The pH value of a neutral solution is 7. An acidic solution has a pH value less than 7, while a basic solution has a pH greater than 7, up to 14.

Pyrogenicity: The tendency of a substance to raise body temperature when injected into the body. Filtration materials that come in contact with injectible liquids must meet Pyrogenicity standards and be classified as non-pyrogenic. Pyrogenicity can be determined by such standard tests as the Limulus Amoebocyte Lysate (LAL) test.

Recovery: Ability of a filter to retain bacteria, DNA or other biomolecules from a solution. Percentage of a chemical or organism population that can be recovered after processing.

Retention: Ability of a filter to retain particles (total number or those of a specific size) suspended in a gas or liquid. In the case of ultrafiltration, refers to the ability to concentrate molecules in solution. Expressed as percent of particles or molecules originally present.

Sanitization, Sanitize: To make clean by removing dirt and other extraneous materials with soap and general disinfectant so as to reduce possibility of growth and spread of pathogenic organisms. A common sanitation agent is 70% ethanol. Bleach is also commonly used.

Sterile, Sterility, Sterilization: To make or be free of any viable microorganisms. Demonstrated by testing to show he absence of growth of microorganisms. If a high bioburden level was present prior to sterilization, pyrogens may still be present afterward.

Thickness: Thickness is typically measured with a gauge called a micrometer and is usually expressed as microns or mils. A micron is a unit of length equal to one millionth of a meter and a mil is a unit of length equal to one thousandth of an inch or .0254 millimeter.

Throughput: The amount of solution that will pass through a filter prior to clogging.

Toxicity Standards: Test to indicate adverse reactions or lethality to drugs or drug components, also used to assess biosafety of filters. Tests include appropriate combinations of direct injection, extraction, and implantation. Generally known as USP biological Reactivity Test.

Vacuum: Depression of pressure below atmospheric pressure. The maximum vacuum possible is about 63.5 cm (25 in.) of Hg.

Water Breakthrough: The amount of pressure required to transmit water through the largest pore of a dry hydrophobic filter. It serves as an indication of pore size for a hydrophobic membrane, and rates a filter’s ability to serve as an aqueous barrier. The larger the pore size, the less pressure is required to push water through the pore. Expressed in the filtration industry in units of pounds per square inch (psi) or bar.

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