A Personal Perspective on the Evolution of Today's LC/MS Techniques

This Account is a personal perspective on the development of the current atmospheric pressure ionization (API) LC/MS techniques. These include atmospheric pressure chemical ionization (APCI), which appeared first, followed by electrospray ionization. Early commercial LC/MS interfaces began to appear in the late 1970s coupled with either electron ionization (EI) or chemical ionization (CI) ion sources, which operated under vacuum. There was an understandable challenge in successfully coupling the HPLC effluent liquid introduction into a vacuum system. The analytical success for the early LC/MS interfaces was slow until John Fenn published his results on the nano flow infusion electrospray analysis with an atmospheric pressure ionization (API) mass spectrometer. Our laboratory was excited about Fenn's report, but we were concerned that the current HPLC techniques operated at mobile phase flow rates much too high for Fenn's electrospray. We commenced studies to increase the ability of electrospray to operate at higher liquid flows by implementing a high flow of nitrogen gas coaxially with the electrospray emitter. This became pneumatically assisted electrospray, which we later called Ion Spray. This technique eventually became commercially available from each mass spectrometer vendor and today is called "electrospray" even though it is actually "Ion Spray".