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James W. Jorgenson of the University of North Carolina at Chapel Hill received the 2011 LCGC Lifetime Achievement award. We spoke to him to talk about his work and his thoughts about the future of chromatography.
Laura Bush, Editorial Director of LCGC and Spectroscopy, presented James W. Jorgenson, the William Rand Kenan, Jr. Distinguished Professor in the Department of Chemistry at the University of North Carolina at Chapel Hill with the 2011 LCGC Lifetime Achievement award. Afterward, she invited him to talk about his career and work.
Your first big breakthrough in the field of separation science was in capillary electrophoresis. What exactly were the limitations of that technique at the time, and how did you approach trying to overcome them?
Jorgenson: Well, I should say that I actually got into capillary electrophoresis in a backwards way. I went to the University of North Carolina intending to do a project on electro-osmotically driven chromatography. There was a paper by Victor Pretorius in the mid-70s proposing this method, where you use electro-osmotic flow to drive chromatography and, as you may remember, that became a pretty popular thing around the year 2000. In thinking about the theory of band spreading in that method, I decided I had to do something simpler to start with so I thought, “Well what’s electrophoresis going to be like in a capillary?” It really wasn’t being done. So I started doing equations on it and realized, to my amazement, that in comparison to chromatography there was only really one mechanisms of band spreading which was longitudinal diffusion, just simple diffusion. I thought, “Why the heck do chromatography? Why not do electrophoresis instead? It looks like the faster you do it the better will work.” That is a rare thing, when you do something faster that it actually works better. So I ended up getting into it backwards like that.
The theory was simple, but experiments were a lot trickier so it took a couple years to really get things going. We had to build our own equipment. Fortunately, fused silica became available as capillary material right at that time. Our initial work was done in glass, which isn’t very UV transparent and UV detection became critical to that.
In doing that work, did you have an “aha” moment?
Jorgenson: Yes, the “aha” moment was seeing that longitudinal diffusion was the only form of band spreading. That made me want to drop anything I was doing and just work on capillary electrophoresis.
You later began working on ultra-high pressures in liquid chromatography, and your work on that topic, first published in 1997, is widely regarded as critical to the success of what is now known as UHPLC. What drew you to that technique?
Jorgenson: It was, in a way, inspired by the 30,000 V being used in capillary electrophoresis, where we took electrophories in gels done in 1000 V and really ramped up the voltage and the performance was dramatically improved. In the mid-1990s HPLC had been around for 25 years at that point and they started at 6000 psi as the limit and sat rock solid there. There was very little contemplation about going higher and there were good reasons not to. They had shown early on in theory, and in some experiments, that if you took a 4-mm bore column and tried running it at very high pressures you’d generate so much heat that it would ruin the separation. So, we thought, “Well we’ve already done this. We had to go to capillaries in electrophoresis to solve the heat problem, let’s do the same thing in LC. Let’s take LC from 6000 psi to 60,000 psi.” We knew if we were going to do this it had to be a big change, not too incremental. Our vision for UHPLC was small particles, long capillary columns. It was going to emulate capillary GC — you would get hour-long runs that were very high efficiency. It was kind of funny to see the commercial equivalent that ending up coming out of that emphasized more of the high-speed aspect of it. So that’s the direction in the practical sense that actually took off.
What do you see for the future of liquid chromatography?
Jorgenson: The funny thing is we started out doing open-tubular liquid chromatography when I started at UNC in 1979. That was one of the things we started and after about 10 years of doing it we dropped it because we could do great separations but the detectors weren’t there. I think liquid chromatography is increasingly mass spectrometry driven. As mass spec has gotten faster and more sensitive, then coupling it to more capable separation methods has become feasible. We are right on the edge where coupling open-tubular columns in LC to mass spec is achievable and the potential there, if you have the sensitivity and speed, is to run circles around a packed bed or a monolithic column, either one. But it’s really going to be tough! The diameter of the columns are sub-5 µm, the flow rates are sub-nanoliter — they are picoliter per minute flow rates — but if the mass spec’s are sensitive enough it’s going to be awesome what can be done there. Millions of plates, easily, and not even needing that high pressure.
This interview has been edited for length and clarity.