Hyperpolarization Update #7 (Well, that worked)

A quick recap: I’m troubleshooting a setup to do hyperpolarization, a technique that allows us to take much faster measurements of chemical samples using NMR (nuclear magnetic resonance, which uses magnets and radio pulses to give you information about chemicals, think MRI) . Hyperpolarization speeds up measurements because it increases the amount of signal you pick up from a targeted chemical, so you have to take less measurements to get the same resolution. Our technique for performing hyperpolarization involves transferring nuclear spins from parahydrogen to our sample. Parahydrogen is a spin state of hydrogen that you make at low temperatures. 

After getting hyperpolarization to work on the big, traditional NMR magnets, it was time to try to get them to work on our small, single-sided NMR magnets. The single-sided magnets we use are quite different from the traditional magnets. They have an open geometry which allows noninvasive, nondestructive measurements of large samples; however, they have a large magnetic field gradient and a small magnetic field. This means that they aren’t great for measuring things like chemical shift, and they have problems with getting signal (the smaller the magnetic field the less signal you get), but they’re great for measuring things like diffusion. The non-destructive nature of the measurements is also pretty useful; you can measure things like the condition of the paint in valuable, old paintings without touching the paint at all.

The setup for producing hyperpolarization on the single-sided NMR is also quite different from the setup for producing hyperpolarization on the larger NMR. Instead of pressurizing a thin NMR tube with parahydrogen and inverting several times, I bubbled parahydrogen through a larger sample vial under a pressure of around 30 psi (the larger sample vial size is necessary to get signal on the single-sided NMR). I figured this system for bubbling would be a major problem, since previous attempts at hyperpolarization seemed to fail to activate the catalyst during bubbling. Activation of the catalyst requires hydrogen to be dissolved in the sample, so I thought that past failures indicated that the bubbling setup was ineffective.

Fortunately, the first time I tried to run the bubbler, I got a color change in the solvent (indicating that the catalyst was activated) after bubbling for about ten minutes and then letting the sample sit for about half an hour. I’m not sure if the setup worked because I was running it at a higher pressure than it had been run at previously, or if the catalyst that I was using now was better than the one that had been used in the past, but it worked.

The next test would involve attempting hyperpolarization on the single-sided magnet. I was really worried about being able to detect signal from the sample. In classic hyperpolarization experiments, the chemical that you are trying to detect (usually pyridine) is extremely dilute, on the order of tens of millimolar (around 2 sample molecules for every thousand solvent molecules). I expected a signal enhancement of about a factor of ten, but even if that happened perfectly, I still wouldn’t be able to pick up signal on the single-sided magnet. One of the characteristics of hyperpolarization is that you have to take all measurements in one scan, since taking a measurement destroys the polarization of your sample. This means you can’t take lots of scans to average out the noise and make the signal more apparent. To get around this problem, I upped the concentration of both pyridine and the catalyst as much as I could. However, I could only dissolve nine times the original amount of catalyst in the solution before it wouldn’t dissolve anymore, so I was still limited to a fairly dilute sample.

Activating the catalyst took a while, probably due to the extremely high concentration of catalyst in the sample. However, after bubbling on and off for almost an hour and a half, I had enough of a color change to feel comfortable moving forward. I set up the parahydrogen generator, bubbled for a couple of seconds in a magnetic field produced by a solenoid, and took a measurement.

And it worked immediately, way better than I expected! (Which is not something that you hear physical chemists saying very often. Murphy’s law is all-powerful.) Not only was I able to detect signal in one scan, it was overwhelmingly huge! (See pictures.)

This is the first clear hyperpolarized measurement we took on the single-sided NMR. (This is a picture from my phone because we were having technical difficulties with saving single-scan data.) Compare to the second figure.

This is the first clear hyperpolarized measurement we took on the single-sided NMR. (This is a picture from my phone because we were having technical difficulties with saving single-scan data for the first couple of measurements.) Note the clear, repetitive, high intensity echo peaks (which are upside-down because that’s how hyperpolarization works). Compare to the second figure.

This is a single-scan measurement of the same sample without hyperpolarization. The signal is completely buried in noise, so what we are measuring is just random fluctuations. In order to get a clear measurement of signal from our sample we would need to take thousands of scans to average out the noise and distinguish the signal, which would take hours.

This is a single-scan measurement of the same sample without hyperpolarization. The signal is completely buried in noise, so what we are measuring is just random fluctuations. In order to get a clear measurement of signal from our sample we would need to take thousands of scans to average out the noise and distinguish the signal, which would take hours, maybe even days.

The next steps are getting ultrafast measurements to work with our hyperpolarization setup, which will allow us to simultaneously measure two different types of relaxation in a sample mixture in one scan (the pulse sequence for this is extremely cool and very elegant but I won’t try to explain it here). I’ll use this to demonstrate that extremely dilute pyridine signal can be easily distinguished when dissolved in non-deuterated methanol. Hopefully that will be functioning by the end of the summer session, and I’ll spend the school year working on applying this new technique to something fun to use for my honor’s thesis. I haven’t found an application yet, but topics I am considering are protein binding kinetics, diffusion in fuel membranes, or even hyperpolarized fluorine (using the new tuneable NMR coil I got working this summer).