Fast 2D Data Collection - NOAH and NUS

One always strives to collect high quality 2D NMR data in a short period of time.  This is particularly important for samples of limited stability or perhaps for monitoring chemical reactions.  High magnetic fields and cryogenically cooled NMR probes have allowed for a higher signal-to-noise-ratio for a given quantity of sample, thereby reducing data collection time as a fewer number of scans are required.  Gradient enhanced 2D NMR data collection gained widespread use in the 1990s.  This represented a tremendous time saving as multi-step phase cycles required for coherence selection could be reduced or eliminated as they were replaced by pulsed field gradients.  Some pulse sequences which required 16 scans per increment to accommodate the necessary phase cycle could be run with a single scan for every increment with the use of pulsed field gradients, thus reducing the data collection time by a factor of 16.  Now, 2D data collection with coherence selection via pulsed field gradients is considered "conventional".  More recently, Non-Uniform Sampling (NUS) was introduced.  Data collection with this technique samples only a limited number of increments in the t1 domain.  The unsampled increments are calculated based on the sampled increments prior to Fourier transformation. The data collection time is reduced in accordance with the number of increments not sampled.  Recently, Kupce and Claridge^1,2 have developed a technique where multiple 2D methods are concatenated in a single super pulse sequence employing a single relaxation delay. They have called the technique NOAH (NMR by Ordered Acquisition using ¹H detection) The time saving of the NOAH technique compared to individually collected 2D spectra results from waiting a single relaxation delay for all experiments rather than a single relaxation delay for each separately acquired spectrum. The data for each spectrum is acquired in separate memory blocks which are separated after data collection allowing the data for each 2D method to be processed individually.  Very recently, both NUS and NOAH have been used together to further reduce data collection times³.  A comparison of the time saving is shown in the figure below for a sample of sucrose in DMSO-d6 collected on a Bruker AVANCE III HD 600 NMR spectrometer equipped with a cryoprobe.

All spectra were collected with 2 scans and a 1 second recycle time.  Individually, both NOAH and NUS offer a significant time saving but when used together they permit very fast, high quality data collection.  A COSY, edited HSQC and HMBC can be collected in a total time of only 4 minutes and 8 seconds.  Other ultra-fast techniques have been developed by others where an entire 2D spectrum is collected in less than one second.

1. Eriks Kupce and Tim D. W. Claridge.  Chem. Commun. 54, 7139 (2018).
2. Eriks Kupce and Tim D. W. Claridge. Angew. Chem. Int. Ed., 56, 11779 (2017).
3. Maksim Mayzel, Tim D. W. Claridge and Ēriks Kupce. Bruker User Library (2018).

Non-uniform Sampling (NUS)

Collecting 2D or 3D NMR data can be very time consuming. The indirect dimension of a 2D experiment is sampled linearly via the t1 increments in the pulse sequence.  An FID must be collected for every single linearly spaced t1 increment. In the interest in collecting 2D or 3D NMR data in a more time efficient manner, a great deal of effort is made towards faster data collection techniques.  While some of these methods are based on spatial selectivity, others are based on sparse sampling techniques in the indirect dimensions of nD NMR sequences.  One such sparse sampling method, given the name non-uniform sampling (NUS), samples a sub-set of the indirect dimension in a random (or weighted random) manner and then predicts the uncollected data based on the data sampled, in much the same way data are predicted in the forward and backward linear prediction methods.  The reconstructed data is then used for the indirect Fourier transforms.  A comparison of the conventional and non-uniform data sampling methods is illustrated in the figure below.

Collecting only a fraction of FID's reduces the experiment time by the same fraction.  The figure below shows a superposition of partial 600MHz ¹H-¹³C HSQC spectra of a D₂O solution of sucrose.

All of the spectra were collected with 2 scans per increment using a 1.5 second recycle time.  The lower spectrum in black was collected conventionally with 256 increments in 15 minutes. The middle spectrum in blue was collected conventionally with 64 increments in 3.75 minutes. The top spectrum in purple was collected using NUS with 25% of 256 increments (i.e. 64 increments) collected in 3.75 minutes.  A comparison of the two conventionally collected data sets shows the expected loss in F1 resolution with the 4-fold reduction in experiment time by reducing the number of increments by a factor of 4. The bottom (black) conventional spectrum and the top (purple) NUS spectrum are however virtually indistinguishable despite the 4-fold reduction in experiment time for the NUS spectrum.  NUS is a very valuable technique for reducing experiment times without sacrificing resolution.