NMR Instrumentation

Instrumentation

J C Lindon

, Imperial College London, London, UK

Introduction

After the ﬁrst observation of bulk phase nuclear
magnetic resonance (NMR) in 1945 and the realiza-
tion that it would be useful for chemical characteri-
zation that came with the discovery of the chemical
shift in 1951, it was only a few years before the ﬁrst
commercial spectrometers were being produced. By
the end of the 1950s, a considerable number of pub-
lications on the application of NMR to chemical
structuring and analysis problems had appeared and
then during the 1960s and later, it became clear that
useful answers could be obtained in biological sys-
tems. Since then the applications and the consequen-
tial instrument developments have diversiﬁed and
now NMR spectroscopy is one of the most widely
used techniques in chemical and biological analyses.
The very high speciﬁcity, the exploratory nature of
the technique without the need to preselect analytes,

and its nondestructive nature have made it very use-
ful despite its lower sensitivity compared to some
other spectroscopic methods.

A general description is given here of the way in

which a modern NMR spectrometer operates, of the
various components that go into making a complete
system, and the particular role that they play. Today,
with the level of computer control present in modern
spectrometers, this naturally includes a description
of both the hardware and software. An overview
diagram of the components of a high-resolution
NMR spectrometer is given in Figure 1.

Components and Principles of
Operation of NMR Spectrometers

Continuous Wave and Fourier Transform Operation

For many years, all commercial NMR spectrometers
operated in continuous wave (CW) mode. This type
of operation required a sweep of the NMR frequency
or the magnetic ﬁeld over a ﬁxed range to bring each
nucleus into resonance one at a time. These scans for

Liquid He fill port

Liquid N

fill port

Liquid He reservoir

Superconducting solenoid

Liquid N

reservoir

Shim coil assembly

Probe

Transmitter frequency
generation and amplifier

Preamplifier

Frequency synthesizer

Local oscillator

Mixer

Amplifier

Computer

Analog

−digital

converter

Lock preamp

Shim power supply,
microprocessor

H lock

transmitter/receiver

compensation

Vacuum

Figure 1

A block diagram of the principal components of a modern NMR spectrometer.

238

NMR SPECTROSCOPY

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H would take typically 500 s to avoid signal distor-

tion. Since most NMR spectra consist of a few sharp
peaks interspersed with long regions of noise, this
was a very inefﬁcient process. A fundamental paper
by Ernst and Anderson in 1966 pointed out the
favorable gain in efﬁciency that could be obtained by
simultaneously detecting all signals. This is achieved
by the application of a short intense pulse of radio-
frequency (RF) radiation to excite the nuclei fol-
lowed by the detection of the induced magnetization
in an RF detector coil as the nuclei relax. The de-
caying, time-dependent signal, known as a free in-
duction decay (FID) is then converted to the usual
frequency domain spectrum by the process known as
Fourier transformation. The efﬁcient calculation of
the digital Fourier transform (FT) requires the
number of data values to be a power of two, typi-
cally perhaps 16 K points for modest spectral widths,
up to 128 K or even 256 K points for wide spectral
widths on high-ﬁeld spectrometers (1 K is 1024 or
2

points). Acquisition of a

H FID requires typi-

cally a few seconds and opens up the possibility of
adding together multiple FID scans to improve the
spectrum signal-to-noise ratio (S/N) since for per-
fectly registered spectra, the signals will co-add but
the noise will only increase in proportion to the
square root of the number of scans. The S/N gain
therefore is proportional to the square root of the
number of scans. This for the ﬁrst time made routine
the efﬁcient and feasible acquisition of NMR spectra
of less sensitive or less abundant nuclei such as

The Magnet and Associated Components

The most fundamental component of an NMR spectro-
meter is the magnet. Originally, this would have been
a permanent or electromagnet and these provided the
usual conﬁgurations for ﬁeld strengths up to 1.41 T
(the unit of magnetic ﬁeld strength is the tesla (T)
equivalent to 10 000 gauss (G)), corresponding to a

H observation frequency of 60 MHz. Because the

sensitivity of the NMR experiment is proportional to
about the 3/2 power of the ﬁeld strength, denoted B

the drive to higher and higher magnetic ﬁelds has
been remorseless. This led the commercial NMR
manufacturers to develop stronger electromagnets
for NMR spectroscopy. This took the highest ﬁeld
strengths to 100 MHz for

H observation, i.e.,

2.35 T. Materials suitable for electromagnets have
maximum saturation ﬁeld strengths at about this
value. Because of the continued need for even higher
ﬁeld strengths, the development of magnets based
on superconducting solenoids was commenced. In
this case, the magnetic ﬁeld is generated by a cur-
rent circulating in a coil of superconducting wire

immersed in a liquid helium Dewar at 4.2 K. This
bath is shielded from ambient temperature by layers
of vacuum and a jacket of liquid nitrogen at 77 K,
which is usually topped up at a weekly interval. A
liquid helium reﬁll is carried out at

B2–3-month in-

tervals depending on the age and ﬁeld strength of the
magnet. The initial development of superconducting
magnets was at 5.17 T corresponding to 220 MHz
for

H and operated in CW mode. Until

B1972, this

represented the highest ﬁeld strength, but then at
regular intervals the available ﬁeld strength gradually
increased along with the emergence of wider bore
magnets enabling the incorporation of larger sam-
ples. Thus, a 270 MHz spectrometer was produced
along with a wide-bore 180 MHz machine and then
the ﬁeld was increased to allow

H observation at

360, 400, 500, 600, 700, 750, and 800 MHz, and the
present limit of any machine yet delivered to a custo-
mer is at 900 MHz (2003). For instruments that
operate for

H NMR at 700 MHz or greater, the

liquid helium bath is kept at

B2 K by a pumped re-

frigeration system so that the higher currents needed
for the higher ﬁelds can be achieved. A modern high-
ﬁeld

NMR

spectrometer

using

this

type

superconducting magnet is shown in Figure 2. One
major achievement has been the introduction of
actively shielded magnets in which the stray magnetic
ﬁeld from the main solenoid is reduced in extent by
opposing magnetic ﬁeld coils. This brings the stray
ﬁeld (e.g., the 5 G limit, outside of which magnetic
metal objects, and people with cardiac pacemakers

Figure 2

A modern high-resolution NMR spectrometer. The

superconducting magnet is shown at the center, in this case
providing a ﬁeld of 21.2 T corresponding to a

H observation fre-

quency of 900 MHz. On the right is the console containing the RF,
other electronics, and the temperature control unit (photograph
reproduced by permission of Bruker Biospin GmbH, Rheinstetten,
Germany).

NMR SPECTROSCOPY

/ Instrumentation

239

should be kept), to

o1.5 m for a 600 MHz NMR

system. This facilitates the adjacent positioning of
other equipment and even allows NMR spectrome-
ters to be much closer to each other than before.
Nowadays, apart from very basic routine low-ﬁeld
spectrometers used, for example, for monitoring
chemical reactions, all NMR spectrometers are based
on superconducting magnets.

At present, 900 MHz for

H NMR spectroscopy is

the current commercial limit and the ﬁrst machines at
this ﬁeld have been produced. Higher ﬁelds must be
on the way and clearly an emotive ﬁgure would be
the 1 GHz

H NMR spectrometer. This development

will require both the design of transmitter and de-
tection technology working at or beyond the limit of
RF methods and developments in superconducting
wire technology. Although the higher ﬁeld strengths
provide greater spectral dispersion and yield better
sensitivity, it may be that some applications involving
heavier nuclei are less suited to such high ﬁelds be-
cause of the ﬁeld dependence of certain mechanisms
of nuclear spin relaxation that could cause an in-
creased line broadening and hence lower peak
heights and delectability.

Inserted into the magnet is the NMR detector sys-

tem or probe. High-resolution NMR spectra are
usually measured in the solution state in glass tubes
of standard external diameters, 5 mm being the most
common, but larger ones (10 mm) are used where
improved sensitivity is required and sample is not
limited. Also, a range of narrow tubes is available for
limited sample studies (4 mm, 3 mm, and even small-
er specially shaped cavities such as capillaries or
spherical bulbs, etc.). Very small sample sizes can be
accommodated in specialized microprobes with sam-
ple volumes in the microliter range. As described be-
low, it is now possible to measure NMR spectra
using special probes in a ﬂow-injection mode avoid-
ing the use of sample tubes completely. The probe
contains tuneable RF coils for excitation of the nu-
clear spins and detection of the resultant signals as
the induced magnetization decays away. A capability
exists for measuring NMR spectra over a range of
temperatures, typically

1501C to þ 2001C.

A major advance in detection of NMR signals has

been the development of probes in which the RF coil
and the preampliﬁer are cooled close to the tempera-
ture of liquid helium, but with the sample remaining
at ambient temperature. These so-called cryoprobes
have a S/N ratio improvement of

B500% over

conventional probes of the same sample diameter.
This is because the thermal noise level in the circuitry
scales approximately as the square root of the ratio
of the absolute temperatures. There are some limi-
tations to this improvement for highly conducting

solutions such as strongly ionic solutions, but these
can be minimized by the use of smaller sample dia-
meters thereby reducing dielectric losses.

Even though modern high-resolution magnets have

very high ﬁeld stability and homogeneity, this is not
sufﬁcient for chemical analysis, in that it is necessary
to resolve lines to about a width of 0.2 Hz and, at a
typical common operating frequency of 600 MHz,
this represents a stability of one part in 3

. This

performance is achieved in two ways. Usually, de-
uterated solvents are used for NMR spectroscopy to
avoid the appearance of solvent peaks in the

spectrum. Deuterium is an NMR active nucleus and
the spectrometer will contain a

H channel for ex-

citing and detecting the solvent resonance. Circuitry
exists in the spectrometer for maintaining this

signal exactly on resonance at all times by detecting
any drift from resonance caused by inherent magnet
drift or room temperature ﬂuctuations and for
providing an error signal to bring the magnet ﬁeld
back on resonance by applying small voltages
through subsidiary coils in the magnet bore. This is
known as a ‘ﬁeld-frequency lock’ and it means that
successive scans in a signal accumulation run are ex-
actly coregistered. To improve the homogeneity of
the magnet an assembly of coils is inserted into the
magnet bore (shim coils). These consist of

B20–40

coils specially designed so that adjustable currents
can be fed through them to provide corrections to the
magnetic ﬁeld in any combination of axes to remove
the effects of ﬁeld inhomogeneities. The criterion of
the best homogeneity is based upon the fact that
when the

H lock signal is sharpest (i.e., the most

homogeneous ﬁeld) the signal will be at its highest.
The currents in the shim coils are usually adjusted
(called shimming), therefore, to give the highest lock
signal. Alternatively, it is possible, although less
common, to shim on the

H NMR signal. This whole

process is now largely computer-controlled in mod-
ern spectrometers. A form of shimming the magnetic
ﬁeld to obtain high homogeneity has arisen from
concepts from magnetic resonance imaging (MRI).
Here, the inhomogeneous magnetic ﬁeld is mapped
in three dimensions initially using the application of
ﬁeld gradients applied along the three orthogonal
axes. Then small currents can be applied to the shim
coils in a computer-optimized fashion over several
iterations of the process. Often for subsequent oper-
ation only the homogeneity along the magnetic ﬁeld
direction needs to be optimized using a single gra-
dient map.

NMR spectra were usually measured with the

sample tube spinning at

B20 Hz to further improve

the NMR resolution. This can introduce signal side-
bands at the spinning speed and its harmonics, and

240

NMR SPECTROSCOPY

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on modern high-ﬁeld machines with improved reso-
lution, this is becoming less necessary and is unde-
sirable in some cases.

In analytical laboratories where large numbers of

samples have to be processed, it is accepted that
automatic sample changers can play a large part in
improving efﬁcient use of the magnet time. These
devices allow the measurement of up to

B120 sam-

ples in an unattended fashion with the insertion and
ejection of samples from the magnet under computer
control. Automatic lock detection and optimization,
sample spinning, NMR receiver gain, and shimming
are also standard. The data are acquired automati-
cally and can be plotted and stored on backing
devices. As an additional aid in routine work, it is
possible to purchase an automated work bench that
will produce the samples dissolved in the appropriate
solvent in an NMR tube starting from a solid spec-
imen in a screw-capped bottle; it will also dispose of
samples safely and wash the NMR tube.

If it is necessary to measure NMR spectra on large

numbers of samples, e.g., from combinatorial chemi-
cal synthesis or from large bioﬂuid studies, then
ﬂow-injection probes are now in general use. Sam-
ples can be made up in 96-well plates using a spe-
cialized robotic system; the plate is then transferred
to a second robotic system in which the contents of
a well can be extracted and ﬂowed into the NMR
probe where the sample is stopped and any NMR
experiments carried out. After measurement, the
sample is then sent back to the same well, to a well in
a different plate, or to waste as desired.

Excitation, Detection, and Computer Processing
of NMR Signals

The RF signal generation is derived ultimately from a
digital frequency synthesizer that is gated and am-
pliﬁed to provide a short intense pulse. Pulses have to
be of short duration because of the need to tip the
macroscopic nuclear magnetization by 90

1 or 1801

and at the same time to provide uniform excitation
over the whole of the spectral range appropriate for
the nucleus under study. Thus, for

C NMR, for

example, where chemical shifts can cover 4200 ppm
this requires a 25 KHz spectral width on a spectro-
meter operating at 500 MHz for

H, which corre-

sponds to 125 MHz for

C. To cover this range

uniformly requires a 90

1 pulse to be o10 ms. The RF

pulse is fed to the NMR probe which contains one or
more coils which can be tuned and matched to the
required frequency, this tuning changing from sample
to sample because of the different properties of the
samples such as the solution dielectric constant. The
receiver is blanked off during the pulse and for a

short period afterwards to allow the pulse ampliﬁer
to ring down. The receiver is then turned on to accept
the NMR signal that is induced in the coil as the
nuclei precess about the ﬁeld and decay through their
relaxation processes. The detection coil is wound on
a former as close as possible to the sample to avoid
signal losses and is oriented with its axis perpen-
dicular to the magnetic ﬁeld. In a superconducting
magnet the sample tube is aligned along the ﬁeld, and
a simple solenoid coil around the sample that would
provide the best S/N is not possible. Consequently,
most detector coils are of the saddle type. However,
in a new generation of microsample coils using the
ﬂow-injection principle it is possible to have the
sample chamber horizontal and hence a solenoid coil
perpendicular to the magnetic ﬁeld can then be used.
The weak NMR signal is ampliﬁed using a pream-
pliﬁer situated as close to the probe as possible, and
then also in the main receiver unit where it is mixed
with a reference frequency and demodulated in
several stages leaving the free induction decay (FID)
as an oscillating voltage in the kilohertz range. This
signal is then fed to an analog-to-digital converter
(ADC) and at this point the analog voltage from
the probe is converted into a digital signal for data
processing. ADCs are described in terms of their
resolution, usually in terms of the number of bits
of resolution, i.e., a typical high-ﬁeld NMR FID is
digitized to a resolution of 16 bits or one part in 2

or 65 536. If only one ADC is used to collect the
NMR FID, it is not possible to distinguish frequen-
cies that are positive from negative with respect to
the pulse frequency. For this reason, the carrier fre-
quency was set to one edge of the spectral region of
interest to make sure that none of the NMR peaks
were ‘aliased’, i.e., folded into the spectral region
from outside it. This had the disadvantage of allo-
wing all of the noise on the unwanted side of the
carrier being aliased onto the noise in the desired
spectral region; hence, reducing the ﬁnal S/N by

O2.

To overcome this problem it is general now to collect
two FIDs separated in phase by 90

1 using either two

ADCs or to multiplex one ADC to two channels.
This approach allows the distinction of positive and
negative frequencies and means that the carrier can
be set in the middle of the spectrum, the hardware
ﬁlters correspondingly reduced in width by a factor
of 2 and an increase in S/N by

O2. This process is

termed quadrature detection. The digital signals can
then be manipulated to improve the S/N ratio or the
resolution by multiplying the FID by an appropriate
weighting function before the calculation of the
digital FT.

Modern NMR spectrometers usually have two

separate computer systems. One is dedicated to the

NMR SPECTROSCOPY

/ Instrumentation

241

acquisition of the NMR FID and operates in back-
ground so that all necessary accurate timing require-
ments can be met. The FID is transferred, either at
the end of the acquisition or periodically throughout
it to enable inspection of the data, to the host
computer for manipulation by the operator. These
computers are based on modern operating systems
such as UNIX or Windows. The computer software
can be very complex and can, like any modern
package, take advantage of networks, printers, and
plotters. Typical operations include manipulations of
the signal-averaged FID by baseline correction to
remove DC offset, multiplication by continuous
functions to enhance S/N or resolution, Fourier
transformation, phase correction, baseline correction
of the frequency spectrum, calculation and output of
peak lists, calculation and output of peak areas
(integrals), and plotting or printing of spectra. NMR
data processing software can also be purchased from
a number of companies other than the instrument
manufacturers, and these often have links to docu-
ment production software or provide output of
NMR parameters for input into other packages such
as those for molecular modeling. A number of ap-
proaches alternative to the use of FID weighting
functions for improving the quality of the NMR data
have been developed and are available from software
suppliers. These include such methods as maximum
entropy and it is possible to purchase these as sup-
plementary items from some NMR manufacturers.

Multiple Pulse Experiments and
Multidimensional NMR

So far everything described applies to the basic one-
dimensional (1D) NMR experiment when the nuclear
spin system is subjected typically to a 90

1 pulse and

the FID is collected. A wide variety of experiments
exist in the literature and are routinely applied to
measure NMR properties such as relaxation times
T

, T

, and T

, which can be related in some cases

to molecular dynamics. These experiments involve
the use of several pulses separated by timed variable
delays and are controlled by pulse programs written
in a high-level language for ease of understanding
and modiﬁcation. The computer system will have
software to interpret the data and calculate the re-
laxation times using least-squares ﬁtting routines.

Such pulse programs are also used to enable other

special 1D experiments such as saturation or non-
excitation of a large solvent resonance (these are dif-
ferent in that the former method will also saturate NH
or OH protons in the molecules under study through
the mechanism of chemical exchange), or the mea-
surement of nuclear Overhauser enhancement effects

that are often used to provide distinction between
isomeric structures or to provide estimates of inter-
nuclear distances. Pulse programs are also used for
measuring NMR spectra of nuclei other than

H and

sometimes in order to probe connectivity between
protons and the heteronucleus. In this case, pulses or
irradiation can be applied on both the heteronucleus
and

H channels in the same experiment. The com-

monest use is in

C NMR where all spin-couplings

between the

C nuclei and

H nuclei are removed

by ‘decoupling’. This involves irradiation of all of
the

H frequencies whilst observing the

C spectrum.

In order to cover all of the

H frequencies, the irra-

diation is provided as band of frequencies covering the

H spectral width; this is consequently termed noise

decoupling or broadband decoupling. Alternatively,
it is possible to obtain the effect of broadband dec-
oupling more efﬁciently by applying a train of pulses
to the

H system, this being known as composite pulse

decoupling.

A whole family of experiments have been deve-

loped that detect low-sensitivity nuclei such as

C or

N indirectly by their spin coupling connectivity to

protons in the molecule. This involves a series of
pulses on both

H and the heteronucleus but allows

detection at the much superior sensitivity of

NMR. Special probes have been developed for such
‘indirect detection’ experiments in which the

H coil

is placed close to the sample, and the heteronucleus
coil is placed outside it, the opposite or ‘inverse geo-
metry’ to a standard heteronuclear detection probe.

The 1D NMR experiment is derived from

measuring the FID as a function of time. If the pulse
program also contains a second time period that is
incremented, then a second frequency axis can be
derived from a second FT. This is the basis for ‘2D’
NMR and its extension to three or even four dimen-
sions. For example, a simple sequence such as

1ð

Þ t

901ð

Þ collect FID for time t

where t

is an incremented delay, results after double

Fourier transformation, with respect to t

and t

, in a

spectrum with two axes each corresponding to the

H chemical shifts. This is usually viewed as a con-

tour plot with the normal 1D spectrum appearing
along the diagonal and any two protons that are
spin coupled to each other giving rise to an off-
diagonal contour peak at their chemical shift coor-
dinates. This simple experiment is one of a large
family of such correlation experiments involving
either protons alone or heteronuclei. The extension
to higher dimensions has already been exploited to
decrease the amount of overlap by allowing spectral
editing and the spreading of the peaks into more

242

NMR SPECTROSCOPY

/ Instrumentation

than one dimension. Hardware and software in
modern NMR spectrometers allows this wide variety
of experiments.

The increasingly complex pulse sequences used to-

day rely on the ability of the equipment to produce
exactly 90

1 or 1801 or any other angle pulses. One

way to do this is to provide trains of pulses that have
the desired net effect of, for example, a 180

1 tip, but

which are compensated for any mis-setting. An ex-
ample of such a ‘composite pulse’ is 90

–180

–90

which provides a better inversion pulse than a single
180

1 pulse. Many complex schemes have been

invented both for observation and decoupling (espe-
cially for low-power approaches which avoid heating
the sample). A universal approach to removing arti-
facts caused by electronic imperfections and which is
also used to simplify spectra by editing out undesired
components of magnetization is the use of ‘phase
cycling’. This allows the operator to choose the phase
of any RF pulse and of the receiver and cycling these
in a regular fashion gives control over the exact ap-
pearance of the ﬁnal spectrum.

For spectral editing purposes or to prove some

NMR spin connectivity, it can be very convenient to
excite only part of a spectrum, possibly only that
corresponding to a given chemical shift or even one
transition in a multiplet. This approach termed
‘selective excitation’ is achieved by using lower-power
pulses applied for a longer period of time (e.g., a
10 ms 90

1 pulse will only cover 25 Hz). Such selective

pulses are often not rectangular as for hard pulses
but can be synthesized in a variety of shapes such as
sine or Gaussian because of their desirable excitation
frequency proﬁles. Modern research spectrometers
can include such selective, shaped pulses in pulse
programs.

Another method for achieving selective detection of

certain types of spin systems is through the applica-
tion of pulsed magnetic ﬁeld gradients. This can be
used to select particular coherence pathways for spins
in a multiple pulse experiment, for example, in multi-
dimensional NMR spectroscopy, to crush unwanted
magnetization such as solvent resonance, to measure
molecular diffusion coefﬁcients, and, hence, to edit
spectra on the basis of the diffusion coefﬁcients of the
molecules giving rise to individual peaks.

Use of NMR Instrumentation

The vast majority of NMR spectrometers are used by
chemists for molecular identiﬁcation purposes in so-
lution, mainly for small organic molecules. However,
NMR spectroscopy can be used in a wide variety of
application areas including macromolecule structure
studies (e.g., proteins, RNA, DNA, polysaccharides),

molecular interaction studies (such as drug–protein
binding), and, of course, in inorganic chemistry
where a wide range of nuclides have been investi-
gated. However, for some applications specialized
instrumentation and methods are necessary and these
areas are summarized here.

NMR of Macromolecules

The determination of the 3D structure of proteins in
the solution state is carried out by molecular modeling
based on distance and angle constraints derived from
NMR spectroscopy. Through the use of extensive

N, and

H labeling procedures, a considerable

number of structures have been obtained. However,
even with the use of such techniques the NMR line-
widths increase as the protein molecular weight in-
creases and it has not been possible to study large
proteins. The main cause of the linewidth increases is
fast T

relaxation caused by dipolar coupling and

chemical shift anisotropy combined with slow mole-
cular motion. However, a technique called trans-
verse-relaxation optimized spectroscopy (TROSY)
overcomes this limitation by making use of cancella-
tion of the transverse relaxation effects between the
dipolar coupling and chemical shift anisotropy. This is
manifested, for example, in a 2D

H–

N NMR spec-

trum that gives four lines for each

H–

N correlation

and TROSY selectively observes only the one com-
ponent that has the cancelled effect and hence a nar-
rower line. This improvement in resolution allows
much larger proteins to be studied. Theory predicts
that the effect is dependent on the magnetic ﬁeld B

and should be complete at 900–1000 MHz, but that
advantage already exists at 750 MHz. The TROSY
technique has enabled structural studies on proteins of
molecular weight 4100 000 Da.

NMR of Solids

Although

H high-resolution NMR spectroscopy is

possible in the solid, most applications to organic
molecules have focused on heteronuclei such as

although there are many published studies of
inorganic systems that use NMR spectra of other
nuclei such as

Si and

Al. High-resolution studies

rely on very short RF pulses, so high-power ampli-
ﬁers are necessary. Similarly, because of the need to
decouple

H from an observed nucleus such as

and thereby to remove dipolar interactions not seen
in liquid state, high-power decoupling is required.
However, the major difference between solution and
solid-state high-resolution NMR studies lies in the
use of ‘magic-angle-spinning’ in the latter case. This
involves spinning the solid sample packed into a
special rotor at an angle of 54.7

1 to the magnetic

NMR SPECTROSCOPY

/ Instrumentation

243

ﬁeld. This removes broadening due to any chemical
shift anisotropies that are manifested in the solid-
state spectrum and any residual dipolar coupling
not removed by high-power decoupling. Typical spin-
ning speeds are 2–6 kHz or 120 000–720 000 rpm,
although higher speeds up to 25 kHz, where the rotor
rim is moving at supersonic velocity, are possible and
necessary in some cases.

Separations Directly Coupled to
NMR Spectroscopy

This has become a major use of modern NMR spec-
trometers, since the technology became commercially
available. Many types of separation have been cou-
pled directly to NMR spectrometers, and also to
mass spectrometers in parallel, for simultaneous
NMR and mass spectrometry analysis and identiﬁ-
cation of eluting materials. Published approaches
where separations have been directly coupled to
NMR spectrometers include solid-phase extrac-
tion, liquid chromatography (LC), capillary LC,
supercritical ﬂuid chromatography, capillary elect-
rophoresis, and capillary electrochromatography.
There is now a large literature on this subject. Ap-
plication areas include impurity proﬁles and their
identity for ﬁne chemicals, identiﬁcation of drug
metabolites, and characterization of natural products
including those of potential medicinal use.

NMR Imaging

A whole new specialized subdivision of NMR has
arisen in the allied disciplines of NMR imaging
(MRI) and NMR spectroscopy from localized
regions of a larger object. Applications range from
the analysis of water and oil in rock obtained from
oil exploration drilling to medical and clinical stud-
ies. Thus, spectroscopic applications include the pos-
sibility of measuring the

H or

P NMR spectrum

from a particular volume element in the brain of a
living human being and relating the levels of meta-
bolites seen in a diseased condition. Some experi-
ments on smaller samples can be carried out in the
usual vertical bore superconducting magnets but
studies are more often performed in specially
designed horizontal bore magnets with a large clear
bore capable of taking samples up to the size of adult
human beings. Because of the large bore, they oper-
ate at lower ﬁeld strengths compared to analytical
chemical applications, and typical conﬁgurations
would be 2.35 T with a 40 cm bore or 7.0 T with a
21 cm bore. Clinical imagers utilize magnetic ﬁelds
up to 3 T with a 1 m bore. Imaging relies upon the
application of magnetic ﬁeld gradients to extra coils
located inside the magnet bore in all three orthogonal

axes including that of B

and excitation using

selective RF pulses. Virtually all clinical applications
of MRI use detection of the

H NMR signal of water

in the subject with the image contrast coming from
variation of the amount of water, or its NMR relax-
ation or diffusion properties in the different organs
or compartments being imaged. Very fast imaging
techniques have been developed that allow movies to
be constructed of the beating heart or studies of
changes in brain activity as a result of light or aural
stimulation to be conducted.

Industrial Analysis

Specialist tabletop machines can be purchased and
these are used for routine analysis in the food and
chemical industries. They operate automatically at
typically 20 MHz for

H NMR using internally

programmed pulse sequences and are designed to
give automatic printouts of analytical results such as
the proportion of fat to water in margarine or the oil
content of seeds.

There have been a number of NMR-based devices

that are used to measure properties of materials that
are located remotely from the NMR magnet. Exam-
ples include the use of specialized devices for oil-well
logging where measurements of NMR parameters
can be made down an oil well, giving information on
the presence of oil and water. Similarly, a device
named the NMR mobile universal surface explorer
(NMR MOUSE) has been developed for applications
in materials science. This can measure relaxation and
diffusion properties of elastomers, industrial coat-
ings, and objects such as rubber vehicle tyres for
quality control purposes.

See also: Chromatography: Overview. Liquid Chro-
matography: Instrumentation; Liquid Chromatography–
Nuclear Magnetic Resonance Spectrometry. Nuclear
Magnetic Resonance Spectroscopy Techniques: Prin-
ciples; Multidimensional Proton; Solid-State; In Vivo
Spectroscopy Using Localization Techniques.