When Ions Head off on their Travels: Opportunities and Challenges in Modern Mass Spectrometry

LP: And the various technologies — how can you put their advantages to use?

Dr. Moehring: In many markets — for instance, taking pesticide analysis as an example – the challenge is to cover as much as possible, ideally in a single analytical procedure. The industry standard for these analytics using LC-MS is analysis with a triple quad MS with targeted screening for designated substances. But I always have a problem with that, if it later turns out there was something in the samples that I didn’t have on my list and therefore wasn’t looking for it. That’s where a full-scan high-resolution approach — the kind you can perform in the Orbitrap system — is better suited. To some extent, you can also look backwards then: did I come across that earlier in my samples, and when did that occur? That has a certain appeal for the foods market, but naturally also for e.g. doping analysis. After all, we hear that more and more these days — medal-winner XYZ at the 2012 Olympic Games in London was later discovered to have this or that substance in their samples. That’s the advantage of full-scan high-resolution systems like the Orbitrap compared to a triple quad. Although I have to say that a triple quad is practically unbeatable in terms of sensitivity.

LP: In the field of lab diagnostics, mass spectrometry has not been on the radar for as long as some conventional procedures. How do you rate its potential in this market?

Dr. Moehring: I believe that clinical mass spectrometry has great potential. The selectivity and sensitivity of mass spectrometry procedures are certainly competitive, and there are already applications in neonatal or vitamin D screening and in medical microbiology that are based on mass spectrometers. I see that as a big potential market. However, here too, you need to look closely at what the customer requirements are. What do we need to offer the customer so that it really functions in a clinical environment? For instance, we have triple quads, including as MD devices. But areas such as precision medicine or translational proteomics are also naturally heading in the direction of diagnostics, and I believe that in the long term the trend will also be towards such devices needing to be registered in the clinical market as MD or IVD devices.

LP: And what are the prospects for miniaturization?

Dr. Moehring: TTransportable, portable, compact devices are definitely issues that excite us. By cooperation with Eawag — Swiss Federal Institute of Aquatic Science and Technology we are currently working on an feasibility study to the issue „Highly time-resolved measurements of micropollutants in different water matrices“. Therfore the mass spectrometer has to get on site.

We have market rivals who are building mass spectrometers as detectors into the LC stack. So miniaturization, ideally whilst keeping the same performance, is also a challenge for product development. How can I get away with less space? I still need to have a vacuum in the device. What do I do with the pumps — do they get smaller with the system, or are they still placed alongside it? That’s very exciting at the moment. Will we progress at some point, say, to where we have a portable handheld device at a port of entry and are able to carry out pesticide analysis there on the spot?

LP: Are there still any markets today where you feel MS is under-represented?

Dr. Moehring: There are areas, for instance in the pharma industry, where today practically everything is still done using chromatographic procedures, even though mass spectrometry would have advantages here too. There’s an example which we call “MS in QC” and which came about in conjunction with a large pharmaceuticals company. Up until now, in order to characterize antibodies in quality assurance their attributes were examined via various chromatographic procedures — e.g. size exclusion, cation exchange and HILIC. We have now developed a multiple attribution method, based on Q Exactive, where we are able to combine a large part of this in a single method via mass spectrometric detection. That is one example of a market where we believe MS is still under-represented. But one where you can use the technology to simplify workflows, for example. The method has already been published and other pharma companies are also expressing interest in it. But, of course, it is a market where they have worked using chromatographic methods for decades and therefore work needs to be done to gain market acceptance.

LP: Are disruptive developments still possible in mass spectrometry?

Dr. Moehring: In an article in 1987, Curt Brunnee described the world of mass spectrometry as an island landscape: with time-of-flight, quad, sector devices, triple quad, ion traps, FT-ICR. Nothing, or barely anything, has changed in that regard in 20, 25 years. And no-one could really imagine another island being added to it. But now there is one: the Orbitrap. To that extent, I won’t rule out something similar happening again. If you go to the major conventions like the ASMS and then look around at the hardware posters and sessions, you see ideas that you might be able to describe as disruptive in 20 years’ time. It doesn’t have to be an analyzer — it could be a new technology for handling the ions on their way to the analyzer. So today you have technologies like FAIMS or ion mobility. There may be technologies here in the future that maybe we cannot imagine today, but which will lead to us becoming much more efficient.

LP: Are there limitations?

Dr. Moehring: Apart from mass spectrometry needing a vacuum? I wouldn’t really call it a limitation, but if we exhibit such a device, then depending on the type of mass spectrometer we have to pump it again somewhere between two hours and overnight until we are ready to take further measurements. Compared to other technologies like HPLC, that is a limitation and there is still room for improvement.

On the other hand, you could of course say for Life Science mass spectrometry: there are procedures that may prove to be faster and simpler at the end of the day for users that we are unable to guarantee, due to the technology that we are using — whether that is the vacuum or the voltage. You definitely should never be under any illusion that everything will stay the same as it is now. In that second where someone has an inspired idea about, say, how you can sequence proteins in a different way to using mass spectrometry and MS-MS, and do so more quickly, more easily and better, Life Science mass spectrometry loses one of its key pillars. And that’s why you should be suitably paranoid when you are looking at the technology roadmap and monitoring technologies which might head in a direction we would describe as sitting in our territory today.

LP: Where will mass spectrometry be at Thermo Fisher in 20 years’ time?

Dr. Moehring: II am absolutely certain that there will be a space for mass spectrometry 20 years down the line. We have technologies that are now tackling entirely new sets of questions in precision medicine, biopharma or clinical mass spectrometry. I believe we will continue to see developments in the key ratios to make MS more attractive for customers. And another area set to develop is bound to be the question of whether compact mass spectrometers will serve as part of an overall solution, perhaps installed at the port or airport for instance, or carried around by every vet in the boot of their car. In those areas, we are sure to see some further exciting developments.

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