A fluid delivery system with flow-based pressure isolation, comprising: a pressurizing device for delivering injection fluid under pressure; a low pressure fluid delivery system; and a pressure isolation mechanism adapted for fluid communication with the pressurizing device and the low pressure fluid delivery system, and comprising: a housing body defining an inlet port, an isolation port, an internal cavity disposed between the inlet port and the isolation port, a seal seat in the internal cavity between the inlet port and the isolation port, and a flow initiating port defining a branch lumen in fluid communication with the isolation port via a branch aperture; a valve member disposed within and free floating in the internal cavity and comprising a disk-shaped body formed of a compliant material having top and bottom projections (140f, 142f) extending from top and bottom sides, respectively, of the disk-shaped body and adapted to center the valve member within the internal cavity, the valve member adapted to move between an open position permitting fluid communication between the inlet port and the isolation port and a closed position preventing fluid flow between the inlet port and the isolation port, wherein the valve member is fluid flow responsive to fluid flow in the inlet port to engage the seal seat and thereby attain the closed position preventing fluid flow between the inlet port and isolation port; characterized by a flow initiating mechanism disposed in a lumen in fluid communication with the isolation port and adapted to initiate fluid flow around the valve member such that the valve member moves to the closed position substantially upon flow initiation, the flow initiating mechanism comprising a flow initiating member disposed and retained within the branch lumen by a retainer and an air inlet prevention filter disposed in a bore defined in the retainer and adapted to prevent air from entering the internal cavity when the filter is wetted with fluid. a pressurizing device for delivering injection fluid under pressure; a low pressure fluid delivery system; and a pressure isolation mechanism adapted for fluid communication with the pressurizing device and the low pressure fluid delivery system, and comprising: a housing body defining an inlet port, an isolation port, an internal cavity disposed between the inlet port and the isolation port, a seal seat in the internal cavity between the inlet port and the isolation port, and a flow initiating port defining a branch lumen in fluid communication with the isolation port via a branch aperture; a valve member disposed within and free floating in the internal cavity and comprising a disk-shaped body formed of a compliant material having top and bottom projections (140f, 142f) extending from top and bottom sides, respectively, of the disk-shaped body and adapted to center the valve member within the internal cavity, the valve member adapted to move between an open position permitting fluid communication between the inlet port and the isolation port and a closed position preventing fluid flow between the inlet port and the isolation port, wherein the valve member is fluid flow responsive to fluid flow in the inlet port to engage the seal seat and thereby attain the closed position preventing fluid flow between the inlet port and isolation port; characterized by a flow initiating mechanism disposed in a lumen in fluid communication with the isolation port and adapted to initiate fluid flow around the valve member such that the valve member moves to the closed position substantially upon flow initiation, the flow initiating mechanism comprising a flow initiating member disposed and retained within the branch lumen by a retainer and an air inlet prevention filter disposed in a bore defined in the retainer and adapted to prevent air from entering the internal cavity when the filter is wetted with fluid. a housing body defining an inlet port, an isolation port, an internal cavity disposed between the inlet port and the isolation port, a seal seat in the internal cavity between the inlet port and the isolation port, and a flow initiating port defining a branch lumen in fluid communication with the isolation port via a branch aperture; a valve member disposed within and free floating in the internal cavity and comprising a disk-shaped body formed of a compliant material having top and bottom projections (140f, 142f) extending from top and bottom sides, respectively, of the disk-shaped body and adapted to center the valve member within the internal cavity, the valve member adapted to move between an open position permitting fluid communication between the inlet port and the isolation port and a closed position preventing fluid flow between the inlet port and the isolation port, wherein the valve member is fluid flow responsive to fluid flow in the inlet port to engage the seal seat and thereby attain the closed position preventing fluid flow between the inlet port and isolation port; characterized by a flow initiating mechanism disposed in a lumen in fluid communication with the isolation port and adapted to initiate fluid flow around the valve member such that the valve member moves to the closed position substantially upon flow initiation, the flow initiating mechanism comprising a flow initiating member disposed and retained within the branch lumen by a retainer and an air inlet prevention filter disposed in a bore defined in the retainer and adapted to prevent air from entering the internal cavity when the filter is wetted with fluid.