Are we sometimes a little too afraid of our instruments? We’re taught not to get our columns dirty, to keep our mass specs clean. This is, of course, generally good advice. There’s also a trend toward modular, push-button instruments – which is perfect for high-throughput labs running very focused methods. If you’re in a contract lab with 25 instruments running 24/7, you want that kind of standardization, automation – and cleanliness. Many analytical scientists will – and do – thrive in those environments. But if you have the luxury of working in a research lab, and the freedom to explore, there’s so much you can do if you really understand your instrument and how to push it – how to make it do things most people haven’t thought of.
You want to know your instruments so well that you can hear when every valve switches. It’s like a patient – you listen to its pulse. You can see it on the pressure trace too: if it’s smooth, things are healthy; if it’s jagged, your “coronaries are clogged,” so to speak. Once you know the instrument like that – almost like a living organism – you can really take it in new directions. And that can lead to discoveries.
To illustrate what I mean, in our PFAS research we’re constantly looking for ways to simplify workflows and extract more information directly from samples. For example, we explore approaches like large-volume injection in LC and GC – whether direct aqueous samples or simple extracts – to improve sensitivity without adding unnecessary cleanup steps. We’re also doing in situ swelling experiments (two-phase partition coefficients) in NMR tubes, and even using thermal desorption tubes like an Easy-Bake Oven to see what volatile PFAS come off materials and products. It’s a bit unconventional, but that’s the point – once you understand your instruments, you can start to use them creatively.
Of course, there are definitely times when cleanup makes sense. For example, we use both low-resolution (triple quadrupole) and high-resolution instruments for our research. With low-res systems, you sometimes have to perform a cleanup step to remove an aromatic contaminant, for instance, and leave the PFAS behind – otherwise, you risk false positives. But if you’re using a high-resolution instrument, you don’t always need that. Adding extra steps just adds time, cost, and potential error – and can actually reduce accuracy and precision.
One area where I think we sometimes default to habit is solid-phase extraction (SPE). It absolutely has its place, and some matrices genuinely require it. But it’s worth remembering that SPE is not free – it comes with significant costs in cartridges, solvents, and waste, especially at scale. And in many cases, it doesn’t remove as much as we assume: it can retain matrix components that will later co-elute with your analytes. In those situations, alternatives like direct injection or large-volume injection can be underutilized options that reduce both complexity and waste. If you really understand your instrument, you can often manage matrix effects in-line using microfluidics and divert valves.
If you’re only working with small amounts of relatively clean water, just inject it directly. And here’s something most people miss: the injection volume. It’s an easily overlooked parameter, but simply increasing injection volume gets more mass to the detector – and better sensitivity. Most people go to all the effort of concentrating a large volume down to 5 mL, then only inject 10 µL. All that time, effort, and money gets thrown away.
Our philosophy is: keep it as simple as possible. Use cleanup steps when they’re genuinely needed, but don’t duplicate them out of habit – that’s just wasted effort. And don’t be afraid of your instruments!
But what if it breaks? Well, it might! But that doesn’t mean you were reckless. If you really know your instrument – if you trick out your autosampler, keep your needle clean, pay close attention to the system – you can make the instrument work for you, instead of the other way around, with relatively little risk. Regardless, instruments break all the time – for everyone. So be bold. Go play. Be creative. Explore.
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