IMHO: Waters systems are more prone to loss of prime (when compared to other major brands). However, they will operate just fine if care is taken each day to prime them before use. It is advised to use the syringe provided to initially prime a dry system and then direct the pump outlet line to waste until the system is fulled primed. You can use transparent Teflon tubing to watch the solvent leave the outlet tube (look for bubbles).
I would suggest checking simple things first.
(1) Perhaps you have not fully degassed your mobile phase. This is critical to prevent cavitation and loss of prime. The mobile phase must not have high levels of dissolved gas. *If you have the 2695E system, then you have the optional vacuum degassing built-in. If this is broken (leak) or not flushed out properly, then problems will result. If you are using the standard helium sparging version, then please make sure you sparge the bottles on a continuous basis, not intermittently.
(2) A leak can cause the introduction of air into the system causing cavitation and/or loss of prime with the pumps. Inspect all lines from the solvent bottles all the way through the system to pump outlet (to find the cause of loss of prime). Check all of the fittings and connections in the remaining lines to the detector's outlet for other sources of leaks which might introduce air. To keep air from getting into the flow cell, route the flow cell's outlet line up against gravity to maintain a small amount of backpressure.
(3) Failing to correctly prime the system (all channels) can also lead to problems.
(4) A stuck check valve (or contaminated one) can also cause loss of prime.
