Femtosecond Pulse Shaping Enables Rapid Two-Dimensional Infrared Spectroscopy

Jul 01, 2013
By Spectroscopy Editors
Volume 28, Issue 7

Why did you start pursuing this technique?

Zanni: Peter Hamm, Manho Lim, and Robin Hochstrasser published the first 2D IR spectrum (1) in 1998 just as I was finishing my PhD. I was thinking ahead to my postdoctoral research and was looking for an emerging research direction that had a lot of potential. I chose well. The first spectra in 1998 were rough, but with technological improvements and a better understanding of vibrations, the field has blossomed. 2D IR spectroscopy is now being used in scientific fields as diverse as materials, biophysics, and nanotechnology, as well as becoming a useful analytical tool.

What types of information can be obtained with 2D spectroscopy that cannot be obtained with one-dimensional IR?

Zanni: With FT-IR spectroscopy you are pretty much limited to absorption frequencies and pattern recognition of the fingerprint region. Two-dimensional IR spectroscopy provides information about connectivity through vibrational couplings and environment through dynamics.

Perhaps the best way to answer this question is to provide some examples. We have studied the transmembrane domain of the M2 proton channel from the influenza virus. The M2 channel is the binding site of amantadine, which is an anti-flu drug that has been used for 40 years. By studying the 2D lineshapes, which provide information about hydration, we were able to determine the residues that line the pore and observed a previously unknown structural change upon channel gating. We were able to determine hydration by creating a photon echo pulse sequence that measured the amount of Gaussian vs. Lorentzian lineshape that contributes to the absorption band. It turns out that Gaussian lineshapes are very sensitive to hydration but Lorentzians are not. It is very difficult to rigorously extract these components from an FT-IR spectrum. Another example is the aggregation of the human islet amyloidpolypeptide (amylin). This peptide self-assembles into long fibers that are associated with type 2 diabetes. As a result, there is an enormous interest in understanding and inhibiting this fiber growth. By monitoring the coupling between strands, we were able to map the mechanism by which these proteins assemble, in what I believe is still the most detailed mechanism for any of the 20 human diseases caused by amyloids (2).

What were the main challenges you had to overcome to make 2D IR spectroscopy work?

Zanni: The main challenge to implementing 2D IR spectroscopy is generating the pulse sequences. In many ways, 2D IR spectroscopy is analogous to 2D nuclear magnetic resonance (NMR) spectroscopy. In 2D NMR, one uses a sequence of radio frequency pulses to measure the coupling between nuclear spins. In NMR, it is quite simple to generate the pulse sequences because radio frequency technology has been around for decades. For 2D IR, most often four laser pulses are required to generate a spectrum. As you might imagine, overlapping four laser beams in space and time is very challenging even for experts in ultrafast spectroscopy, especially considering that mid-IR laser beams are invisible to the naked eye.

My research group made two contributions that helped solve this technical barrier. First, we showed that one does not need four separate beams, but that two would suffice. Using two beams also eliminates a whole bunch of other difficulties associated with producing the highest resolution spectra with the proper phasing so that positive peaks point up and negative peaks point down. Second, we invented a way of computer programming the laser pulses, so that pulse sequences can be generated with ease and on the fly, without having to rearrange optics. We can now collect spectra in seconds that used to take hours. Our approach is now being used by many research groups across the world. It simplifies the spectrometer to such an extent that my former postdoctoral researcher Dr. Chris Middleton and I have started a company together to commercialize pulse shapers and 2D IR spectrometers, which is called PhaseTech Spectroscopy, Inc.

How exactly does mid-IR pulse shaping work?

Zanni: Femtosecond pulse shaping was invented about 20 years ago to manipulate visible laser light. There are a number of different ways of doing it in the visible, and several research groups tried to extend those methods into the mid-IR, but with limited success. One of the original ways, but possibly the most under appreciated, was by Professor Warren Warren. He used an acousto-optic modulator that filtered the spectrum of the laser light. He tailored the sound wave in the modulator with an arbitrary waveform card and thus could computer program the pulse shapes. We mimicked his approach, but used an acousto-optic modulator made of germanium so that it would work directly in the mid-IR.

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