A gasket for actuating a pump cassette, the gasket having a first side configured for placement against a pressure delivery block and having an opposing second side configured for placement against a flexible cassette membrane overlying the pump cassette, the gasket having a main body and an elastomeric valve actuation region that moves outward toward the cassette under positive pressure and inward toward the pressure delivery block under negative pressure; the valve actuation region configured to be positioned adjacent a valve actuation portion of the cassette membrane overlying a cassette valve of the pump cassette; the valve actuation region comprising: a central portion configured to align with and to be pressed against a valve seat defining an orifice (184, 186, 190, 192) of the cassette valve; a peripheral portion configured to extend over a valve chamber (183, 185, 189, 194) of the pump cassette surrounding the valve orifice (184, 186, 190, 192); a vacuum channel forming a perimeter around at least a portion of the peripheral portion of the actuation region, the vacuum channel defined by an inner wall contiguous with the peripheral portion of the actuation region, a floor, and an outer wall contiguous with or formed from the main body of the gasket, the vacuum channel being open to the second side of the gasket; the vacuum channel fluidically connected to a vacuum port in the gasket that penetrates from the second side to the first side of the gasket, the vacuum port configured to communicate with a corresponding pressure delivery block vacuum port when the gasket is positioned against the pressure delivery block; characterized in that, the inner wall of the vacuum channel is configured to flex toward the pressure delivery block when the gasket valve actuation region is placed under negative pressure, at least partially collapsing the inner wall of the vacuum channel while the valve actuation region moves inward and is pulled away from the cassette valve orifice (184, 186, 190, 192) when the pump cassette is present against the gasket. the gasket having a first side configured for placement against a pressure delivery block and having an opposing second side configured for placement against a flexible cassette membrane overlying the pump cassette, the gasket having a main body and an elastomeric valve actuation region that moves outward toward the cassette under positive pressure and inward toward the pressure delivery block under negative pressure; the valve actuation region configured to be positioned adjacent a valve actuation portion of the cassette membrane overlying a cassette valve of the pump cassette; the valve actuation region comprising: a central portion configured to align with and to be pressed against a valve seat defining an orifice (184, 186, 190, 192) of the cassette valve; a peripheral portion configured to extend over a valve chamber (183, 185, 189, 194) of the pump cassette surrounding the valve orifice (184, 186, 190, 192); a vacuum channel forming a perimeter around at least a portion of the peripheral portion of the actuation region, the vacuum channel defined by an inner wall contiguous with the peripheral portion of the actuation region, a floor, and an outer wall contiguous with or formed from the main body of the gasket, the vacuum channel being open to the second side of the gasket; the vacuum channel fluidically connected to a vacuum port in the gasket that penetrates from the second side to the first side of the gasket, the vacuum port configured to communicate with a corresponding pressure delivery block vacuum port when the gasket is positioned against the pressure delivery block; a central portion configured to align with and to be pressed against a valve seat defining an orifice (184, 186, 190, 192) of the cassette valve; a peripheral portion configured to extend over a valve chamber (183, 185, 189, 194) of the pump cassette surrounding the valve orifice (184, 186, 190, 192); a vacuum channel forming a perimeter around at least a portion of the peripheral portion of the actuation region, the vacuum channel defined by an inner wall contiguous with the peripheral portion of the actuation region, a floor, and an outer wall contiguous with or formed from the main body of the gasket, the vacuum channel being open to the second side of the gasket; the vacuum channel fluidically connected to a vacuum port in the gasket that penetrates from the second side to the first side of the gasket, the vacuum port configured to communicate with a corresponding pressure delivery block vacuum port when the gasket is positioned against the pressure delivery block; characterized in that, the inner wall of the vacuum channel is configured to flex toward the pressure delivery block when the gasket valve actuation region is placed under negative pressure, at least partially collapsing the inner wall of the vacuum channel while the valve actuation region moves inward and is pulled away from the cassette valve orifice (184, 186, 190, 192) when the pump cassette is present against the gasket.