Expert Insight: Ambient ionization mass spectrometry in space and time: From high-throughput analysis to molecular imaging

Explore the applications and benefits of ambient ionization for biomedical research and its future potential for pharma and food industries

11 Dec 2020

Prof. Zoltan Takats, Ph.D., Imperial College London

In this SelectScience webinar, Prof. Zoltan Takats, Imperial College London, explores the utility of rapid evaporative ionization mass spectrometry (REIMS) in the pharmaceutical and food industry as well as in synthetic biology. Takats also discusses the analytical performance of desorption electrospray ionization (DESI) MS, one of the most popular approaches for mass spectrometric imaging. DESI is compared to other desorption ionization methods and its applications are reviewed in areas including cancer research, drug analysis and the imaging of formalin-fixed paraffin-embedded samples. A brief description of the data analysis workflows associated with these individual applications is also covered.

Catch up on this webinar to learn:

  • Ambient ionization mass spectrometry techniques and applications for biomedical research
  • Advantages, benefits, and opportunities of ambient ionization coupled mass spectrometry imaging/molecular profiling
  • Applications of REIMS and benefits of DESI in mass spectrometry imaging
  • The current state of ambient ionization in biomedical research and future potentials

Think you’d benefit? Register now and read on for highlights of the Q&A session.

Q: Did you try AP-MALDI imaging in combination with REIMS?

ZT: Yes, we have tried atmospheric pressure (AP) matrix-assisted laser desorption/ionization (MALDI) with the REIMS atmospheric interface in multiple different ways. For one way, we simply prepared a surface for MALDI and introduced the MALDI plume into the instrument, which worked well. The other way, which was a bit more interesting, involved mixing various analytes with the MALDI matrix and creating an aerosol out of this fine powder, before aspirating it with the REIMS interface. This also worked well. It works a bit better with matrices that work well for infrared MALDI, but in general, there is a high similarity between the different ionization mechanisms.

Q: What specific benefits does the DESI approach provide?

ZT: One main advantage is the lack of sample preparation compared to other techniques such as MALDI, for example. Also, if you look at the spectral coverage, in the case of hydrophilic metabolites, DESI is certainly a better choice. In the low-mass range, where MALDI spectra are usually full of matrix fragments, adducts of fragments, etc., DESI spectra can be very clean, and we can actually detect lots of low-molecular-weight, hydrophilic metabolites and practically all core carbon and energy metabolites that belong to this group.

Q: Can I do multiple DESI experiments on the same sample?

ZT: Absolutely. Generally, when it comes to DESI imaging, you can reimage the sample multiple times. You can actually do positive and negative on the same sample, and can change solvents, and so on and so forth. This is a really nice feature of DESI and we do it often.

Q: What do you see for the future of this imaging approach in the next two to five years?

ZT: I think that the imaging approach will become significantly more robust, especially due to the work we've been doing regarding creating the droplet guns. This will also allow us to go down to a few micrometers in resolution, so single-cell imaging will certainly be possible. Another interesting thing, as we develop the DESI technology, is the strict division between DESI and secondary ion mass spectrometry (SIMS) will become a bit blurred. I can see that there will be low-pressure DESI experiments, or you could call it multiple-charge, water-cluster SIMS, for higher resolution. I think this is the main direction for the technique, going towards SIMS and getting much better spatial resolution and robustness, as well as towards high-speed imaging. I can imagine that we will be able to do hundreds of pixels per second in two to five years.

Q: Can DESI be applied to cell culture?

ZT: Yes, we can certainly do that, but there are two basic caveats. One is the gas flow. In the case of REIMS, we have a very gentle helium flow which blows the cell culture medium apart, so we have a little island that we can sample. In the case of DESI, we have a close-to-sonic-speed nitrogen jet, so if there is a medium, it will be all over the place. Also, certain cell cultures, especially certain fast-proliferating cancer cell lines, tend to come off the surface, thanks to the high-velocity gas jet and often the heated capillary. We have had some success, but with the caveats of using DESI for cell culture analysis, we moved to various REIMS approaches, at first bipolar forceps, and later on to infrared lasers. The infrared laser solution is much easier and can work at a much higher throughput, plus, if we are using 3-micrometer resonance lasers, the chemical coverage is quite comparable.

Q: What type of molecules do not work well with DESI?

ZT: There’s nothing that simply wouldn't work, but it does depend on how you perform the DESI experiment. If you do a direct comparison with MALDI, intact protein analysis is certainly a weakness. I'm not saying that we cannot detect intact proteins, Helen Cooper's group recently published a series of papers on the various intact proteins detected from tissues. But certainly, if we are lucky, we can detect a handful of intact proteins from a place where we know they are. While in the case of MALDI, if we choose the right matrix and right conditions, we can actually detect hundreds. I think that's where the sharpest contrast is.

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