Air-Water Binary Gas Integrity Test for Sterilizing and Virus Filters

Abstract

Reliability of retention performance is of paramount importance for membrane filters designed for sterile and virus filtration. To achieve dependable retention, an integrity test can be applied to ensure the absence of oversize pores or defects that can compromise the retention capability of the filter. Probably the most commonly applied nondestructive integrity test for membrane filters is the gas-liquid diffusion test, with air and water often used as the gas-liquid pair. However, the sensitivity of the air-water diffusion test is limited by the fact that the diffusive flow rate for an integral membrane can span a range that is large compared to the flow contributed by a defect. A novel nondestructive air-water integrity test for microporous and nanoporous membranes is introduced here that provides improved test sensitivity by measuring the gas composition in addition to gas flow rate. Oxygen permeates through water faster than does nitrogen, so with air as the challenge gas and water as the wetting fluid, the permeate stream will be enriched in oxygen. The permeate oxygen concentration is predictable, accurately measurable, and within a narrow and repeatable range for an integral membrane. A leak through the membrane will result in a deviation from the integral permeate concentration, signaling a defect. Compared to the conventional air-water diffusion test, this air binary gas (i.e., O₂ and N₂) test in which the permeate gas composition is measured (in addition to the diffusive flow rate) has a superior signal-to-noise ratio and was demonstrated to provide a significantly higher level of retention assurance for both sterilizing grade and virus filters. Because air and water are used as the gas-liquid pair, the air binary gas test also maintains the convenience, safety, and environmentally friendly aspects of the air-water diffusion test.

LAY ABSTRACT: To ensure that sterilizing and virus removal filters are free of defects, an integrity test is often conducted both before and after use of the filters. In the commonly used air-water diffusion integrity test, pressurized air is applied to the water wetted filter and the air flow rate across the filter is measured. A flow rate above a specified limit indicates a leak through the filter. The sensitivity of the test is limited by the level of background noise (integral flow rate) relative to the leak signal (excess flow rate). An enhancement to the air-water diffusion test is introduced here in which the sensitivity of the test can be improved by measuring the composition of the diffused gas. Oxygen permeates through water faster than does nitrogen, so the permeating gas will be enriched in oxygen. Compared to the flow rate, which can span a range of values for integral filters, the integral oxygen concentration is well defined, so even small deviations from the expected concentration signal a leak. Because air and water are used as the test materials, the developed approach achieved higher sensitivity without sacrificing the convenience, safety, and environmentally friendly aspects of the air-water diffusion test.