Sensitivity improved experiments

FySy), where = E", (Schleucher et al., 1994). This Hamiltonian can be implemented using a heteronuclear Hartmann-Hahn mixing sequence that creates an effective Hamiltonian = 2TrJ f (FySy + F S ) that is embedded between two 9(f I,S)y pulses. A heteronuclear isotropic Hartmann-Hahn (HIHAHA) transfer step (Quant et al., 1995a Quant, 1996) can be used for in-phase COS-CT, for example, from S to F (Sattler et al., 1995a). CQS-CT mixing steps yield sensitivity-improved experiments and are especially useful for experiments that are based on gradient echoes. 

Practical constraints prevent this technique from living up to its potential, even in this, the era of the superconducting probe. Until sensitivity improves by at least another order of magnitude, the INADEQUATE experiment will remain just that - inadequate by name and by nature. 

Dalvit, C., et al., Sensitivity improvement in 19F NMR-based screening experiments theoretical considerations and experimental applications. J Am Chem Soc, 2005, 127, 13380-13385. 

The second (sine) term produced by the evolution delay has all the information we need—it is antiphase 13C coherence labeled with the 13C chemical shift in t —but it is lost because its phase (S ) causes it to be unaffected by the 90° 13C pulse at the end of t. Effectively we are throwing away half of our signal at this point. A new method was developed to save this wasted signal and boost the sensitivity of HSQC and many other experiments. These modified pulse sequences are called sensitivity enhanced or sensitivity improved (Bruker adds si to the pulse sequence name) and the strategy is called preservation of equivalent pathways (PEP) because the two terms are equivalent except for their phase. 

Since Coulomb forces decay much more slowly than van der Waals forces, an EFM experiment can be performed even without any feedback, if the sample roughness is low compared to the tip-sample distance. Terris et al. used this technique for the first time to investigate a contact electrification of a metal-insulator system [355-357]. Later, further improved experiments on contact electrification with single charge sensitivity were performed by... 

LSPR-based sensitivity enhancement using surface-relief nanostructures has been confirmed experimentally in a few smdies to date. In the experiments conducted by Byun et al. [26], ethanol-water mixture at varied ethanol concentration was used to estimate the sensitivity enhancement by periodic nanowires atA = 200 nm and 500 nm respectively as 44% and 31% over conventional structures, as shown in Fig. 7. Note that the sensitivity enhancement for bulk index measurement is relatively limited compared to layered bio-molecular interactions, because of reduced index contrast against ambience. It was also found that surface roughness can degrade sensitivity performance [27]. Measurement of the DNA hybridization process was performed using nanoposts at A = 110 run and presented more than fivefold sensitivity improvement, as shown in Fig. 8 [28]. 

Sensitivity improved gradient experiments are available, however, the increased length of the pulse sequences allows for dephasing of the desired magnetization. Therefore, the theoretical sensitivity enhancement is not always obtained. Furthermore, the sensitivity improvement is often restricted to a particular spin system (usually one I spin and one S). 

Up to a 90° phase shift in both frequency dimensions (which can be easily corrected for), the two resulting spectra are almost identical. Because the noise of the two spectra is uncorrelated (Cavanagh and Ranee, 1990b), it is increased only by a factor of yfl if the two spectra are added, whereas the signal is increased by a factor of 2. Overall, a sensitivity improvement of /2 can be achieved in the PEP version of the TOCSY experiment, relative to experiments where one of the two transverse magnetization components is simply eliminated. 

In addition to sensitivity-improved two-dimensional TOCSY experiments, PEP versions of two-dimensional HSQC-TOCSY experiments (Cavanagh et al., 1991) as well as three-dimensional HSQC-TOCSY and three-dimensional TOCSY-HMQC experiments (Palmer et al., 1992 Ranee, 1994 Krishnamurthy, 1995) have been reported. This enhancement scheme is also used in heteronuclear coherence-order-selective coherence transfer (COS-CT Schleucher et al., 1994 Sattler et al., 1995a). Because in... 

HETCOR and COLOC involve C detection these have been superseded by more sensitive Undetected HMQC, HSQC, and HMBC experiments, which provide ca. 30-fold sensitivity improvement over C detection. Heteronuclear correlation experiments provide simpler spectra (a single peak is observed for each C-H attachment) and they take advantage of the much greater C spectral dispersion. 

TROSY element based on DD/ C CSA compensation. Sensitivity improvement of triple resonance experiments for nucleotide bases... 

There are a few ways of linking the techniques of LC-MS and LC-NMR. The most common method is in a parallel mode by splitting the flow, e.g. 50 1, so as to direct the majority of it to the NMR due to its relative insensitivity. This means that the analytes are detected simultaneously by both detectors and possibly also by UV, which may actually be used as the trigger to begin detection by the NMR and MS modules. Alternatively, the rapidly acquired MS data can be used to direct the NMR experiments or vice versa. A second method of interfacing the two techniques is to use the serial mode or stopped flow mode, which enables more sensitive NMR experiments to be carried out. A recent development in stopped flow NMR is the inclusion of in-line solid phase extraction (SPE) after the LC. The SPE acts as a fraction collector for individual compounds. This trapping/ washing step can improve sensitivity several fold. A third method is fraction collection, where samples from the LC are collected in a loop for analysis later, perhaps after certain data have been reviewed. 

Kozmiriski and Nanz" reported the development of the HECADE experiment that allowed the determination of heteronuclear coupling constants from E-COSY-type crosspeaks. A sensitivity improved HSQC-HECADE pulse sequence has since been developed by the same authors." The HSQC-based GSQMBC experiment reported in 1997 by Sklenaf and coworkers,and discussed in Section 3.3.3, has also been used for the measurement of small, long-range heteronuclear coupling constants. 

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