Signal enhancement for the sensitivity-limited solid state NMR experiments using a continuous, non-uniform acquisition scheme

Abstract

We describe a sampling scheme for the two-dimensional (2D) solid state NMR experiments, which can be readily applied to the sensitivity-limited samples. The sampling scheme utilizes continuous, non-uniform sampling profile for the indirect dimension, i.e. the acquisition number decreases as a function of the evolution time (t1) in the indirect dimension. For a beta amyloid (Aβ) fibril sample, we observed overall 40 ~ 50% signal enhancement by measuring the cross peak volume, while the cross peak linewidths remained comparable to the linewidths obtained by regular sampling and processing strategies. Both the linear and Gaussian decay functions for the acquisition numbers result in similar percentage of increment in signal. In addition, we demonstrated that this sampling approach can be applied with different dipolar recoupling approaches such as radiofrequency assisted diffusion (RAD) and finite-pulse radio-frequency-driven recoupling (fpRFDR). This sampling scheme is especially suitable for the sensitivity-limited samples which require long signal averaging for each t1 point, for instance the biological membrane proteins where only a small fraction of the sample is isotopically labeled.

An analysis of NMR sensitivity enhancements obtained using non-uniform weighted sampling, and the application to protein NMR

“…We note however that small SNR improvements can translate into more substantial reductions in acquisition time. When coupled with rapid recycling experiments such as the SOFAST-HMQC, we expect that these methods may be of utility for the study of challenging and sensitivity-limited samples, such as solid-state NMR [17], solution-state NMR of proteins or metabolites at natural abundance [14,22,23], or large, dilute systems such as ribosome nascent-chain complexes [24,25]. 1.11 1.22 Table 1: Calculation and comparison of the relative sensitivities of uniform and non-uniform weighted sampling for three commonly applied window functions, w(t), computed for a signal, s(t), with a relaxation constant T 2 and observed for an acquisition time T aq , expressed in terms of the dimensionless ratio τ = T aq /T 2 .…”

“…The approach may also be useful for sensitivity-limited solid-state NMR experiments [17]. However, it is important to note that acquisition with a non-uniform sampling density has the same effect on signal intensities as applying a window function to uniformly sampled data (Fig.…”

Sensitivity of Nonuniform Sampling NMR

“…In this report, NUS means the samples are selected from the Nyquist grid and are each acquired with the same number of transients, but NUS has been further generalized with respect to sample phases, 14 while a strategy of acquiring different numbers of transients on the uniform grid 10 has been revisited. 15,16 …”

Magic Angle Spinning NMR Spectroscopy: A Versatile Technique for Structural and Dynamic Analysis of Solid-Phase Systems

“…74 A variant of nonlinear data sampling also includes collecting data points in indirect dimensions using variable number of scans per point resulting in sensitivity enhancements albeit at the expense of spectral resolution. 75,76 …”