You know you’re getting older when techniques that you used to use constantly are in danger of becoming lost arts. The one that I’m thinking about today is thin-layer chromatography, or TLC. This is a classic lab method, taught to generations of undergraduates and used by untold hordes of working organic chemists. And it’s slowly on the way out.
Before we go into what’s killing it, a brief bit of background for the non-chemists in the crowd. To do a TLC, you take a plate of glass (or something else stiff, like thick aluminum foil) that’s been coated with a thin layer of some finely ground solid. The usual choice is silica gel, which is basically very pure, very finely ground sand. In its powdered state, it resembles a slightly grittier form of corn starch. In the old days, you’d spread this stuff out on the plates yourself, but it’s been twenty years since I saw anyone do that. During my whole career, you’ve been able to buy them premade, in all sorts of variations.
Then you take a drop of your mixture and put it on the silica layer, down near the bottom of the plate. Once it dries, you stand the thing up in a beaker or jar that has some solvent in the bottom - the idea is to wet the plate at the bottom, but not so far up that it rinses off your spot. As the silica gel layer wets, the solvent creeps up the plate. And (as in all the other forms of chromatography), the various compounds in your mixture will travel faster or slower, depending on their interactions with the silica versus with the solvent. A strong polar solvent (methanol) will tend to whip everything up with the solvent front, and a wimpy one (hexane) will tend to leave everything back at the start. Adjusting the solvent mixture can give you a spread of spots up and down the plate once you've let it run for a bit, and you can see those with a UV lamp, or by dipping the plate in some reagent that will generate colored material from your compounds. Excellent pictures of the process can be found here.
TLC is cheap, fast, convenient, and can be run in untold different variations. So what's killing it? Something even faster, more convenient, and more powerful: liquid chromatography/mass spectrometry. That was just barely possible when I was in grad school, and was expensive and tricky when I was in my early years in the industry. But now the machines, while still not cheap, are everywhere, and they're used in walkup mode. Just enter your data - or link it over from your electronic lab notebook - put your sample vial in the rack, and go away. What you get back is a better separation than TLC can give you, and every peak/spot now can be checked for the masses of the compounds in it. You can ask all the possible questions, such as "which peak has the mass I'm looking for?", or "What the heck is the main mass in that peak, anyway?". The mass spec gives you more information than you can deal with, and it's all stored digitally for your later perusal and second thoughts.
This trend has been coming on for years now, but it's reached a very noticeable point. Even a comparatively old-school guy like me hardly runs TLC plates any more. Once in a while, I'll need to, but mostly, it's just "throw it on the LC/MS". And I get the impression that people coming through grad school now are losing the finer points of TLC completely. And why not? They've never had to worry about them at all. . .