A novel non-destructive integrity test for microporous and ultraporous membranes has been developed that is far more sensitive to detecting defects than a conventional gas-liquid diffusion test. The test developed here uses a binary gas mixture and is based on the principle of differing gas permeabilities through the liquid layer of a wetted membrane that results in a concentration enhancement of the faster permeating gas. In an integral membrane, the permeate composition can be predicted based on the transport properties of the gases permeating through the liquid layer and the known operating conditions. A deviation from the expected concentration is an indication of the presence of a defect or open pores. Unlike the gas-liquid diffusion test, the binary gas test has low sensitivity to membrane porosity, liquid layer thickness, and membrane area. Consequently, integral devices will exhibit a relatively narrow range of test values, resulting in a superior defect signal-to-noise ratio. In this study, a binary gas integrity test method was developed and applied to a newly developed virus clearance filter. The binary gas test was demonstrated to provide a significantly higher level of virus retention assurance compared to the air-water diffusion test, and can be implemented by the filter manufacturer as an additional quality assurance test prior to shipping the product to users. (C) 2008 Elsevier B.V. All rights reserved.