The methods and devices disclosed provides for the delivery of agents to an orifice cavity and subsequent aspiration of the agent and orifice contents from the orifice cavity and related areas. In one form, the delivery and aspiration system comprises an agent delivery sub-assembly, an aspiration sub-assembly and a device tip sub-assembly. The subassemblies operate to first deliver an agent contained within the device to an orifice cavity and after an optional time delay, subsequently aspirate the delivered agent and orifice contents from the orifice cavity and related areas. In another form, a removable reservoir is provided whereby the aspirated agent and orifice contents from the orifice are assayed either independent of or within the device itself.