An Inside Look at Nearfield Infrared Spectroscopy

Pittcon 2026 has officially gotten underway in San Antonio, Texas. As one of the media partners for the conference, Spectroscopy is conducting various interviews with several key speakers.

In our first interview conducted before Pittcon 2026, we sat down with Seth Kenkel, who is a postdoctoral research associate at the University of Illinois Urbana-Champaign. At Pittcon, Kenkel is set to deliver a talk titled, “Innovations in Null-Deflection Scanning Probe Infrared (NDIR) Imaging for High-Sensitivity, High-Resolution Molecular Analysis.”¹ His talk will cover how nanoscale infrared (IR) spectroscopic imaging offers label-free, super-resolved chemical insight for biomedical applications but is hindered by probe–sample coupling and other physical effects that distort quantitative interpretation.¹ Kenkel will explain how the null-deflection scanning probe infrared (NDIR) technique addresses these limitations by minimizing measurement artifacts, enabling stable and accurate nanoscale molecular imaging for applications such as cancer research and drug discovery.¹

Kenkel’s background is in engineering. After earning his B.S. and M.S. degrees in mechanical engineering from the University of Illinois at Urbana-Champaign, he worked in manufacturing, spending two years in the Construction and Forestry Division at John Deere.² It was after his time at John Deere that Kenkel went back to school to earn his doctorate in engineering.

Kenkel is currently working on nano-infrared imaging using atomic force spectroscopy and quantum cascade lasers, and we sat down with him to talk about this current research.

Pittcon 2026 is shaping up to be an interesting conference. Can you talk about what you personally are looking forward to at the show?

This is actually my first time attending Pittcon. I planned on attending during Covid, but it got canceled. Because this will be my first time, I want to mainly visit the exhibitors and am interested in looking at the nearfield spectroscopy progress and see what progress other researchers are making in the field. That's always interesting.

On the exhibitor side of things, I look forward to seeing what companies are showing this year, such as Photothermal Spectroscopy Corp and see what other technologies and innovations are out in the market.

Can you provide an overview of nearfield IR spectroscopy and what this technique is best suited for?

Nearfield IR spectroscopy is a higher resolution IR spectroscopy imaging technique with resolution beyond the conventional diffraction limit. This technique is best for measuring native chemical signals in different samples, like polymers, cells, and materials, without using labels. We mainly apply it to imaging subcellular molecules, such as metabolites in single cells, and we are interested visualizing molecules that can't be labeled without altering their use in the samples, such as metabolites or drugs.

Your work identifies probe–sample mechanical coupling as a major confounding factor in near-field IR measurements. How does this coupling physically distort nanoscale infrared signals, and why has its impact on biochemical interpretation been historically underestimated?

It’s a factor that's multiplied by the underlying spectroscopic signal. This is a multiplicative effect originating from the mechanical coupling of the cantilever with the sample. So, with these techniques, you’re usually creating some sort of dynamic AC modulation or mechanical oscillation signal in this cantilever at its mechanical resonant mode to get a much higher signal. The problem, though, is that the resonance of the cantilever is very sensitive to any small changes in the mechanical coupling to the sample. What this does is adds a scaling factor that changes every sample position. Traditionally, these conventional systems have been successful at measuring spectroscopic signals by going to a single point and looking at the spectra. But when you try to map that spatially and scan one absorption band across the sample, you can get a large masking effect. You're going to get two images that overlay on top of each other. One's mechanical contrast, which depends on structural and mechanical features of the sample such as height and stiffness. In terms of visualizing where the IR absorbing molecules are in the sample, when you're looking for really small concentrations of molecules or weak absorbers, it can get drowned out by the mechanical contrast.

The null-deflection scanning probe infrared (NDIR) technique is introduced to minimize measurement distortions. How does NDIR differ operationally from conventional nanoscale IR approaches?

Yeah, that's a good question. NDIR is a custom technique that we developed in my graduate work, which basically uses an additional vibration underneath the sample generated by some mechanical actuator. It uses that as a reference so you can create a constant reference vibration, moving the entire sample up and down at some oscillation and get that to match the current vibration that's induced by the chemical absorption or the IR absorption effect. If you can now control this vibration and match it to the IR with equal amplitude, you can generate zero deflection in the cantilever itself. In this state of zero deflection, you know that the reference vibration is directly equal to the IR vibration and neither of those depend on probe sample mechanical coupling. Thus, you can read out the signal provided to the reference actuator and bypass issues associated with cantilever detection that limits the ability to visualize weak chemical species in the samples.

Can you share examples of how NDIR improves molecular mapping in cancer or drug-discovery contexts?

We’re currently working actively on that. We've shown in the past a couple examples of significant improvements imaging native chemical contrast in fixed cells that are prepared with standard transmission electron microscopy protocols. We have demonstrated that the NDIR technique improves chemical contrast accuracy, so we can now visualize molecular signals in these types of epoxy embedded cell samples, and we're currently applying this to image different metabolites inside of cells and drugs. We are currently developing a number of experiments in which we culture cells with different metabolites such as glucose and have demonstrate the ability to visualize where they go through the cells. We're in the process of extending this capability to detect multiple metabolites simultaneously.

What remaining technical or theoretical challenges must be addressed before nearfield IR spectroscopy becomes a routine tool in biomedical research and clinical translation?

On our end, we have this prototype system that we would always like to make more sensitive, repeatable, and faster with better functionality. For instance, if we collect multiple images at different wavelengths representing different molecular species, it's kind of useless if they don't overlap because the images might drift on the order of nanometers over time, resulting in fine structures not registered to each other. So, we've been developing ways to improve the acquisition speed and overall performance of those measurements and get them read out in parallel, so that they're automatically registered to achieve repeatable nanoscale molecular imaging. We've made a lot of progress on that technology recently. The next part is how to apply that information. There's a lot of rich detail in these signals, and obviously you can qualitatively tell whether it is a glucose band or a protein band. We need to figure out how to translate that to material identification and build a pipeline to collect repeatable data and then process and quantify these signals to get more quantitative measurements.

References

1. Pittcon, Innovations in Null-Deflection Scanning Probe Infrared (NDIR) Imaging for High-Sensitivity, High-Resolution Molecular Analysis. Pittcon.org. Available at: https://app.swapcard.com/event/pittcon-2026/planning/UGxhbm5pbmdfNDMwMzg5NA== (accessed 2026-02-25).
2. University of Illinois Urbana-Champaign, Dr. Seth Kenkel. UIUC.edu. Available at: https://chemimage.illinois.edu/group-members/postdocs/seth-kenkel/ (accessed 2026-02-25).