NMR is a non destructive technique and so reducing acquisition time can be used either to increase sample throughput, or to lower the detection limit. To lower the detection limit a given amount of time is used to acquire a greater number of scans than would normally be acquired. A relatively recent method for reducing acquisition time is ASAP (Acceleration by Sharing Adjacent Polarization)1. The ASAP technique speeds acquisition by greatly reducing the length of the relaxation delay.
All NMR experiments include a relaxation delay, a period in which the magnetization is allowed to relax back to thermal equilibrium. The relaxation delay is executed before every scan. In nearly all cases, a relaxation delay of one second is used in the Facility's standard parameters.
The figure below shows the pulse sequence diagram for a standard HMBC in blue at the top, and for an ASAP-HMBC in red at the bottom. Normally these pulses sequence diagrams are just used to indicate timing and are not drawn to scale, but in this case the horizontal axis has been drawn to scale and indicates time in seconds. In the standard HMBC the relaxation delay of one second takes about 2⁄3 of the time taken to record a scan (1.35 s). In the ASAP-HMBC a short 25 ms TOCSY spinlock period (the solid red block), is introduced and the relaxation delay is much shorter (30 ms) reducing the total acquisition time (0.40 s) to about a third of the standard HMBC.
In a heteronuclear experiment on a natural isotopic abundance sample, signal is only detected from protons attached to 13C. The protons attached to 12C do not contribute to the signal and remain at thermal equilibrium. The spinlock period in the ASAP-HMBC mixes the polarization of all the protons, effectively transferring equilibrium magnetization from 12C-attached protons to the 13C-attached protons and allowing the relaxation delay to be greatly reduced.
The ASAP technique can only be applied to heteronuclear experiments on samples at natural isotopic abundance but ASAP-HSQC2 and ASAP-HMBC3 experiments have already been published. The main drawback of ASAP experiments is that the acquisition period now takes up the majority of the time to record a scan. For experiments that use composite pulse decoupling during acquisition (like HSQC and H2BC) this leads to heating. A recent attempt4 to minimize this problem used chunked data acquisition which enabled the decoupling to be turned off for parts of the acquisition. This reduced heating but complicated data processing.
Overall, ASAP is a simple technique that offers significant reductions in acquisition time. It can also be used in conjunction with non uniform sampling and the combination of these two techniques should yield much faster experiments and decreased detection limits.
1. Erics Kupce, Ray Freeman
"Fast multidimensional NMR by polarization sharing."
Magn Reson Chem. 2007 45(1):2-4.
2. David Schulze-Sünninghausen, Johanna Becker, Burkhard Luy
"Rapid Heteronuclear Single Quantum Correlation NMR Spectra at Natural Abundance"
J. Am. Chem. Soc. 2014 136(4):1242-1245
3. Julien Furrer
"A robust, sensitive, and versatile HMBC experiment for rapid structure elucidation by NMR: IMPACT-HMBC"
Chem. Commun. 2010 46(19):3396-3398
4. Ikenna E. Ndukwe, Alexandra Shchukina, Krzysztof Kazimierczuk, Carlos Cobas, Craig P. Butts
"EXtended ACquisition Time (EXACT) NMR-A Case for 'Burst' Non-Uniform Sampling"
Chemphyschem 2016 17(18):2799-2803