By Mathew J. Dunleavy and Michael A. Mansfield, PhD
Hydrophobic membrane can be seen incorporated in a number of medical device applications, including bag, tubing, vial, pump and IV vents, and insufflation devices.
At a Glance
The choice of membrane depends on several factors, including the conditions of the intended application, degree of sterility assurance required, chemical compatibility, biocompatibility, and the degree of hydrophobicity and/or oleophobicity. Consideration should also be given to the desired methods of device fabrication and sterilization. In the following presentation, a review of vent membrane properties is offered.
Filtration applications which sterilize and remove moisture from gases include respiratory therapy filters, which prevent transmission of infectious agents via patient cross-contamination in ventilators. Bacteria and other particles are removed from gas streams feeding insufflation filters used in laparoscopic surgical procedures. Smoke and aerosols are removed by plume filters used in laser surgery and electro-cauterization. In venting, gas pressure is relieved through a hydrophobic membrane filter which blocks the path for liquid leakage in ostomy and urine drainage bags and IV flash-back vents. Venting is also used to prevent air from entering a patient’s bloodstream in intravenous (IV) solution filters.
The vent membrane selection process includes a comprehensive review of the material's intended use.
Selection CriteriaThe first consideration when selecting a membrane is its intended use. The various fluids that may interact with the membrane (e.g., water, buffer, protein or other drug, blood, urine, feces, etc.) have different surface tensions and, therefore, varied tendencies toward wetting out the membrane and causing failure. The physical geometry of the system in operation must also be considered. In some instances, a vent membrane is always above the liquid surface and remains dry, while in others, the fluid may contact the membrane.
Environmental conditions during use, such as temperature, pressure, and pH could potentially affect the interaction between membrane and fluid. The smaller the membrane pore size, the more resistant it will be to wetting out under pressure. Also, duration of intended use for the filter must be investigated. For example, a vent membrane on a 96-hour IV filter (typically 0.1 µm) must be resistant to wetting for longer periods than an IV flashback vent (typically 0.8 µm) used for only minutes.
|Characteristics of filter materials|
The degree of sterility assurance varies with membrane pore size. In liquid filtration, the standard method for claiming sterilizing grade is the microbial challenge test, defined by ASTM F838-83. The acceptable result is complete retention when challenged with B. diminuta (ATCC 19146) at a minimum concentration of 107 organisms per cm2 of membrane. In general, membranes with pore sizes of 0.22 µm or less are considered sterilizing grade. While there is no standard test method for mycoplasma retention, 0.1 µm membranes are rated by some suppliers for removal of these organisms. Because of the critical nature of some applications and the risk of harm to patients from membrane wetting and subsequent microbial passage, many medical device manufacturers use 0.1 or 0.2 µm pore sizes for their vent membranes. IV filters and transducer protectors are two examples.
The mechanism of bacterial retention by hydrophobic membranes in a gas stream is different than that for hydrophilic membranes in liquid. Bacteria and other pathogens do not float freely in air; rather they are attached to particles (aerosol or dust). In gas applications, infectious agents can be rejected by membranes with pore sizes larger than the pathogens. Membranes with pore sizes up to 5.0 µm are claimed to have more than 99.99% bacterial retention efficiency by some suppliers. Similar claims exist for viral retention on 0.2 µm membranes. Therefore, membranes with larger pore sizes are used in less critical applications, yielding the benefits of higher flow performance or reduced cost because less material can be used.
Chemical and biological compatibility requirements also influence the choice of membrane. Chemical compatibility between the membrane and the fluids to which it will be exposed must be determined to ensure that chemical attack and failure of the membrane do not result. Biocompatibility is an even more important criterion, as the membrane and its extractable components must be non-toxic. The standards for biocompatibility are defined in NF EN ISO 10993: Biological Evaluation of Medical Devices. These include cytotoxicity, hemolysis, sensitization, and pyrogenicity. This also includes USP Class VI testing of plastics, for systemic toxicity, intracutaneous toxicity, and implant.
The degree of hydrophobicity of the membrane must be considered. The liquids that must be repelled and the operating conditions affect membrane choice. Suppliers offer materials that are hydrophobic (resist wetting by aqueous fluids), oleophobic (resist wetting by oils), and super-hydrophobic (resist wetting by alcohols).
To utilize a membrane in a medical application, it must be fabricated into a device. Several methods can be used to attach membranes to devices. Heat sealing, where the device material is melted and forced into the pores of the membrane, requires materials of sufficiently different melting points to ensure good penetration without melting the membrane. Ultrasonic welding involves the melting and joining of materials by high frequency vibration, with the device plastic either intruding the membrane or trapping it in a seal geometry. This approach works best when the membrane and device are similar polymers because an integral ultrasonic seal between dissimilar materials can be difficult to achieve. The seal geometry must take this into account to ensure that a mechanical, pinch-type seal is formed around the membrane.
Lastly, insert molding or over-molding is a technique where a secondary molding operation simultaneously seals the membrane into the device and attaches device components to each other. This approach offers the benefits of increased automation, reduced manufacturing cost, and increased quality. As with ultrasonic welding, pinch-seal geometry is used to ensure an integral membrane seal.
In all cases, a method of determining device integrity should be used. Not only must it be shown that acceptable membrane has been used to fabricate the device, but also that the seal of the membrane to the device is integral. No pathway larger than the pore size of the membrane is permissible. Integrity test methods include air pressure hold or decay tests, aerosol or solid particle challenge tests, and bubble point tests. Some tests are destructive, while others allow actual use of the tested product. In any case, devices should be validated by microbial retention testing to support a retention claim. Integrity test methods must be correlated to microbial retention.
The intended method of sterilization for the finished product also affects membrane choice. Today, gamma irradiation and exposure to ethylene oxide (EtO) gas are the two most common methods, although electron beam (E-beam) sterilization is growing in popularity. Autoclave or steam sterilization is still used for some products. Not all materials are compatible with all sterilization methods.
Membrane Materials Overview
- Polytetrafluoroethylene (PTFE) is a widely used material in medical venting and gas filtration. It is an inert material that offers excellent flow properties and high chemical resistance. Dimensional instability of cut shapes of this membrane type can cause difficulties in robotic handling in over-molding operations. PTFE is incompatible with gamma or E-beam sterilization because chain scission causes loss of integrity when the material is exposed to ionizing radiation.
- Polyvinylidene fluoride (PVDF) is a durable material that offers good flow properties and broad chemical resistance. It is available in both natural and super-hydrophobic forms.
- Ultra-high molecular weight polyethylene (UPE) is a more recent entry into the medical venting and gas filtration market. It is a naturally hydrophobic material that offers excellent flow properties and broad chemical resistance.
- Modified acrylic membrane treated to be hydrophobic is an economical choice for venting applications. It is oleophobic, hydrophobic, and chemically compatible.
ConclusionHydrophobic polymeric membrane filters play important roles in medical devices. Several factors must be considered in selecting the right material. These include the conditions of the intended use, the degree of sterility assurance required, chemical and biological compatibility, and device fabrication and sterilization methods. A thorough review of these criteria will help ensure that the correct material is chosen for these critical applications.
ONLINEFor additional information on the technologies and products discussed in this article, visit Millipore Corp. online at www.millipore.com. 
Mathew J. Dunleavy is the senior marketing manager for OEM Business Development at Millipore Corp., 80 Ashby Rd., Bedford, MA 01730. He has over 20 years experience in the development and commercialization of polymeric membrane based filtration products for medical, laboratory, and life science applications. Dunleavy holds a BS in bioengineering and an MS in chemical engineering from Columbia Univ. and an MBA from Northeastern Univ. He can be reached at 781-533-2150 or email@example.com .
Michael A. Mansfield is the applications development manager for the Membrane and Media OEM Group at Millipore. He has over 16 years of product and applications development experience in membrane separations technologies. Mansfield holds a BS in biology from Rollins College, an MS in botany from Oregon State Univ., and a PhD in plant molecular biology from the University of Georgia.