Originally published March 1997
A microporous membrane is a thin, flat sheet of polymeric material, superficially resembling paper, that contains billions of microscopic pores. Depending on the membrane, these pores can range in size from 0.01 to more than 10 µm. Microporous membranes are available in both hydrophilic (water-filtering) and hydrophobic (water-repellent) forms. This article will be limited to the discussion of microporous hydrophobic membranes (MHMs). Numerous polymers can be employed to form MHMs. Today, the predominant polymers used are PTFE (polytetrafluoroethylene), polypropylene, PVDF (polyvinylidene difluoride), and acrylic copolymer. All of these polymers can be treated in order to obtain specific surface characteristics that can be both hydrophobic and oleophobic (repelling liquids with low surface tensions, such as multivitamin infusions, lipids, surfactants, oils, and organic solvents).
Microporous hydrophobic membrane--shown in roll at top--is used in products such as (clockwise from left) a vented blood warmer, an in-line suction filter, a vented suction container, and a transducer protector. Photo: W.L. Gore & Associates, Inc.
MHMs block liquids, while allowing air to flow through the membrane. They are also highly efficient air filters, eliminating potentially infectious aerosols and particles. Widely used in medical devices, a single piece of MHM can replace mechanical valves or vents. The unique properties of MHMs enable design engineers to improve the performance of existing medical devices and enhance the designs of new, emerging products. In addition, the proper incorporation of MHMs can often reduce product assembly costs, improving profits and the cost/benefit ratio to the patient.
The low surface tensions of MHMs cause them to repel fluids from the surface, leaving the pores of the membrane filled with air. The porosity of the membrane allows air to flow freely through the material. Because of their diverse surface tensions and microstructures, membranes made from various polymers have significantly different properties, including chemical inertness, water-entry pressures, airflows, and surface release characteristics (see Figures 1 and 2).
Figure 1. Water-entry pressures of various common membrane materials.
MHMs can filter aerosols and particles from air with high efficiency, and can block potentially contaminated liquids, acting as efficient viral barriers. It is important to note that these membranes are not filtering viruses out of liquids. Rather, they are blocking the liquids that contain viruses and filtering virus-laden aero-sols from air. In any vent or barrier design, it is necessary to choose a membrane that will not allow passage of a liquid at the given application pressure, since liquids may carry infectious particles. As long as the liquid and aerosols are contained, the membrane acts as a sterile barrier, protecting the device or equipment and, ultimately, the patient or health-care worker.
Figure 2. Airflow versus pressure drop for various common membrane materials.
MEDICAL DEVICE APPLICATIONS FOR MHMs
Engineers have solved many device design problems with MHMs. A single MHM layer, with no moving parts, can substitute for a combination of valves and filters. Applications include, but are not limited to, in-line sterile barriers (transducer protectors, vacuum-line protectors, gas analyzers), liquid shutoff valves (suction canister vents), air inlet valves (IV spike vents), air vent valves (IV filter vents), container filling vents (urine bag vents), sterile wound dressings, sterile vent barriers on packaging, gas sterilization devices for insufflation and blood oxygenation, and aerosol containment units for chemotherapy drug reconstitution.
In-line sterile barrier devices are used in tubing to protect equipment from cross-contamination. In a fluid-handling system such as a dialysis machine or hospital suction pump, fluid must be contained, while the safe operation of the system often depends on the ability to accurately measure pressure. The hydrophobic nature of an MHM prevents fluid from passing while allowing air to flow freely across the membrane, facilitating accurate pressure measurements. The MHM can also be designed as a viral barrier to block infected aerosols and particles, keeping any contamination upstream of the filter barrier. When a procedure is finished, the contaminated barrier and tubing are discarded and replaced, while the downstream system remains sterile.
Many collection devices contain some type of liquid shutoff valve to prevent leakage of contaminated fluids when the container is full. Suction canisters collect body fluids that may be infectious. A mechanical valve is commonly used, but has numerous shortcomings: for example, it can stick and not let air through, or it can seat improperly and allow fluid to leak. A mechanical valve will not stop infected aerosols from passing, so the canister is often followed by an in-line filter. Deploying an MHM in the suction canister eliminates the need for this costly combination of a mechanical shutoff valve and in-line filter.
In devices such as IV-delivery systems, a solution must drain from a container at a prescribed rate. With a rigid solution container, air must flow into the system through an air inlet valve as the liquid drains in order to prevent a vacuum from forming in the container. In current systems, a valve or vent is placed at the bottom of the container. During fluid delivery, air flows into the system; when the system is shut off, liquid sits on the valve or vent, and no air enters. Many such devices use a mechanical ball check valve, which can occasionally stick or leak. When an MHM is used as the air inlet valve, eliminating the mechanical valve, the membrane prevents the liquid from leaking out of the container while providing a sterile barrier that filters the air entering the container. Air inlet valves can be made more economically and with a greater assurance of satisfactory performance when MHMs are incorporated.
Intravenous or intraarterial filtering systems use a hydrophilic filter to remove bacteria, particulates, and air from parenteral solutions. Air bubbles--residing in solutions or resulting from the repriming of the filter system--can collect on the upstream surface of the hydrophilic membrane and create an air lock, preventing parenteral solution from reaching the patient. The filtering systems require air vent valves that vent air bubbles before they reach the hydrophilic membrane filter. MHMs have historically provided an optimal solution for air vent valves in intravenous and intraarterial filtering systems.
A fluid-collection device such as a urine bag also requires a vent to facilitate sterile air displacement as the collection container fills. An MHM can be incorporated into a collection container to ensure the sterile passage of contaminated resident air, while preventing any of the collected fluid from leaking into the environment.
Used as sterile wound dressings, MHMs are often superior to conventional wound dressing materials. In order to promote healing, wounds require air circulation. Conventional dressings permit air to circulate but do not filter out airborne pathogens that can infect a healing wound. In contrast, MHMs can offer a barrier that is permeable to air and yet will remove airborne pathogens and provide for the sterile containment of wound exudate.
In today's world, more effective--and at times more aggressive--
measures are being explored for sterilizing packaged products. One result has been that MHMs have been found to be an excellent alternative for use as sterile vent barriers on packaging. New sterilization techniques are necessitating far more robust alternatives to conventional packaging vent materials. The need for bacterial/viral barriers is leading many packaging engineers to specify MHMs. One emerging application is the use of an MHM vent on containers used for freeze-drying sensitive materials, such as human tissue and pharmaceuticals.
Many medical procedures require the introduction of a gas into either an anatomical structure or a device that is exposed to body fluids. To prevent infection, filters are needed for gas sterilization. Nonshedding MHMs can sterilize any gas used in a medical procedure over a wide range of pressures and airflow requirements, and can also prevent the incursion of any liquid that may be pres-ent--ensuring that a sterile, dry gas is delivered to the patient. For example, insufflation filters used in laparoscopic surgery feature MHMs that efficiently filter the gas introduced to inflate the abdomen and repel any returning fluid.
Many procedures performed by health-care workers today can be dangerous if care is not taken. One particular area of concern is the reconstitution of toxic drugs, such as those used in chemotherapy. When the diluent is added, a positive pressure builds up in the sealed drug vial. Aerosols containing the reconstituted drug can be released when the septum is punctured, exposing personnel to potential dangers. By incorporation of an MHM either into the vial's rubber stopper or into a needlelike assembly, the pressure in the vial can be vented and any aerosols contained.
The choice of a particular MHM depends on a number of design considerations. As with any design requirements, there will need to be trade-offs in order to achieve the proper cost/benefit ratio. Design engineers should take into consideration the following issues before making their MHM selection.
Membrane Application. Is the MHM intended to retain fluids, aerosols, or particles? In a pure air-filtration application, one should choose the media that will provide the highest airflow for the required filtration efficiency. The particle to be filtered (bacteria or virus-containing aerosol or particle) and the particle's size should be specified. For vents that must contain fluids in addition to filtering particles from air, see below.
Fluid Containment. The pores of an MHM vent are always filled with air. The fluid that is contained by the vent must not be able to penetrate the pores ("wet out" the membrane) under any use condition. If the fluid wets a pore, the vent will no longer serve as a bacterial barrier.
Fluid Surface Tension. MHMs work because of the difference in surface tension between the fluid and the polymer making up the MHM. A high-surface-tension fluid, such as water, will be attracted to itself rather than to the membrane polymer: to reduce its surface area in contact with the membrane, it will bead up and refuse to enter the pores. The greater the difference in surface tension, the more pronounced this repellent action will be. Low-surface-tension fluids--such as blood, urine, or multivitamin infusions--may require membranes with reduced surface tensions to prevent the liquid from wetting the pores.
Fluid Operating Pressure. Although the fluid is repelled from the surface of the MHM, elevated pressures can force it into and through the pores. The larger the pore size, the easier it is to force liquid into the pores. Because a vent must not leak, the first factor to consider is the water-entry pressure of the membrane. The design engineer should ask the MHM manufacturer to specify the minimum water-entry pressure of the membrane. A typical or average water-entry pressure will not be useful to the device designer, since the vent must hold the liquid over the membrane's entire range of variation of water-entry pressure.
Airflow Rates. Once the membranes that are capable of holding the required liquid-entry pressure are found, the one that will give the highest airflow through the membrane should be selected. Because devices usually require venting a certain quantity of air at a given pressure drop (P) over a given time, such a selection will provide the device designer with the choice of maximizing airflow through a given surface area or reducing the surface area of the vent. The airflow through a vent is proportional to the P over most ranges of pressure seen in medical devices. The MHM manufacturer should specify the minimum airflow through the vent (per area at a given P). Once again, knowing the typical or average airflow is not sufficient, since the MHM must vent the required amount of air over the membrane's entire range of variation of airflow.
Surface Area. Designers should always consult with MHM manufacturers before finalizing the plans for a product, in order to avoid a design with inadequate surface area for venting.
Temperature. Because high temperatures may damage some membrane constructions, one should be aware of any extreme temperature requirements associated with an application.
Housing Material. Designers should always know in advance what housing material the MHM is to be sealed to, as well as the intended sealing method. There are several approaches to forming a hermetic seal to an MHM. These include ultrasonic welding, heat sealing, RF welding, and even self-adhesive patches. The choice depends on the selection of housing material, the MHM, and the nature of any challenges to the seal integrity. The suppliers of the MHM and of the sealing equipment should together be able to advise on the best process.
Sterilization Method. MHMs can be sterilized by autoclaving, ethylene oxide, or gamma irradiation. The MHM manufacturer should be consulted to determine the best approach to use with each type of membrane.
Membrane Physical Demands/ Life Expectancy. Some applications of MHMs--such as a pulsed vacuum or repeated cleaning and reuse--put considerable physical stress on the membrane. Extreme service conditions of this type should always be brought to the attention of the MHM manufacturer.
Biocompatibility. The designer should be sure that the selected MHM meets the biocompatibility requirements of the device.
Chemical Compatibility. The MHM should remain unchanged in use by any expected chemical exposure, such as contact with drug formulations or cleaning solutions.
Membrane Quality/Consistency. The physical properties of any MHM (water-entry pressure, airflow, thickness, etc.) have a certain amount of in-lot and lot-to-lot variability, which depends on the process used to manufacture the membrane. The specifications for the MHM will take this into account. MHM quality refers to the manufacturer's ability to provide defect-free membranes within the specifications. Consistency refers to the amount of variation inherent in the process of making the MHM. Both of these characteristics will affect the final device.
Micrograph (5000*) showing 0.2-µm expanded PTFE membrane material.
Custom Capabilities. While standard products can serve in many applications, certain new designs require properties that are not possessed by existing commercial MHMs. If the size of the application justifies the development costs, new MHMs with unique properties can be custom developed. Designers should ask the membrane supplier if such services are available.
Supplier Quality/Service. It is important for designers to choose a supplier that has knowledgeable, responsive field engineers and support staff to answer any questions that arise. The MHM supplier has experience in the field that can be helpful to the process of developing a client's product. The design engineer should not hesitate to work together with the MHM supplier from the initial design stages through the production of the final device.
There are many parameters used to characterize the functional attributes of specific MHMs. Listed below are some of the key terms and their definitions.
Water-Entry Pressure (WEP). Also known as water breakthrough, WEP is the pressure required to force water through a hydrophobic structure. This property is typically expressed in pounds or bars per square inch.
Gurley Value. This variable provides a reliable measure of the airflow through an MHM. Usually expressed in seconds, the Gurley value will describe the length of time a specific volume of air under a specific pressure takes to pass through a specific area of an MHM.
Bubble Point. Used to characterize the MHM's reference pore size, the bubble point is the lowest pressure that is required to displace a low-surface-tension fluid from the pore structure of an MHM, and is typically expressed in pounds or bars per square inch. The MHM must be tested with a low-surface-tension fluid that can enter the pores, such as isopropanol. Because MHMs are hydrophobic, water will not enter the pores. Therefore, MHM bubble-point tests cannot be conducted with water, as is typically done for hydrophilic membranes.
MHMs can be sealed to plastic devices using several different methods. Depending on the device material and the polymer makeup of the MHM, alternatives can include ultrasonic welding, radio-frequency (RF) sealing, heat sealing, insert molding, or adhesive bonding.
Ultrasonic Welding. Ultrasonic welding of MHMs should be carried out with 20-kHz or, preferably, 40-kHz machines using high frequency and low amplitude settings. Welding should employ a radiused energy director, with vibrations dampened through cushioning of parts. Multiple far-zone welds should be avoided.
RF Sealing. RF sealing can only be used with MHM polymers having the correct dielectric properties.
Heat Sealing. For heat sealing to be effective, the materials of construction of the MHM should have melt temperatures comparable to those of the housing materials. Adequate seal land area must be ensured, and nonstick coatings must be used on all sealing dies if the MHM is a meltable polymer.
Insert Molding. The temperature limitations of the MHM will dictate the temperature of the resin injected. Using spring-loaded shutoff pins will help guard against crushing the MHMs.
Adhesive Bonding. MHMs can be cut to any required shape and supplied with contact adhesive for convenient assembly.
MHMs VERSUS HYDROPHOBIC DEPTH MEDIA
Product designers can choose between using MHMs or using depth media that have been rendered hydrophobic by a secondary chemical process. Historically, some device designers have selected hydrophobic depth media because of their high flow rates and low cost. However, hydrophobic depth filters have serious limitations. First, depth-media filters have extremely low water-entry pressures, cannot be used to contain liquids in any of the higher-pressure applications, and may become blocked due to water incursion, even under lower pressures. Second, depth-media filters can only be nominally rated for their pore sizes--they cannot be "bubble-pointed." Because depth media depend on the density and thickness of the media to entrap particles, they can sometimes unload the trapped material under higher differential pressures or when the media become saturated.
Finally, depth media have the potential for media migration. The fibers making up the depth media can actually end up in the effluent, and ultimately in the patient.
We have briefly described the properties, common applications, design considerations, key test definitions, and sealing recommendations for microporous hydrophobic membranes. The health-care industry is continually looking for new technologies to improve patient and worker safety and, at the same time, reduce costs. Protection of parenteral fluids from airborne contaminants, prevention of cross-contamination of devices and equipment, and protection of workers from contaminated liquids, aerosols, and body fluids are among the main areas of concern. Incorporating MHMs into medical devices and equipment is a cost-effective and scientifically proven approach to protecting patients and those who provide care for them.
Wendy Goldberg is a product specialist at W.L. Gore & Associates, Inc. (Elkton, MD), where she is reponsible for developing products for a variety of medical venting applications. She previously held positions with Ciba Geigy and Merck. Also at Gore, Mary Tilley has spent more than 20 years in material and membrane processing and development as well as in handling a wide range of medical filtration and venting applications. Jim Rudolph specializes in medical filtration products at Gore and consults with numerous medical device companies on how to optimize the marketing of filtration devices to hospitals.