FORREST A. NELSON Varian Associates, Palo Alto, Calif. CHARLES A. REILLY and WILLIAM E. SAVAGE Shell Development Co., Emeryville, Calif.
Process Monitor Using High-Resolution Nuclear Magnetic Resonance High resolution NMR permits rapid analysis of some hardto-measure chemicals as they flow in a process plant HIGH-resolution nuclear magnetic resonance, NMR, is a powerful analytical tool for determining the structure of organic compounds. Its principle was first observed independently by Bloch (7) and Purcell ( 4 ) in 1945. Some years later it was discovered that, with a better magnet, the single resonance line from an isotope could often be resolved into a spectrum of several lines whose intensities and relative positions depend upon the structure of the molecule. The process monitor described uses this technique of high-resolution NMR (3, 5 ) . The problem involves continuous measurement of the ratio of two organic compounds. The instrument itself was constructed in 1955, and operational tests were conducted during 1956 and later. In this system the composite spectrum is swept each 6 seconds, and the output signal is recorded continuously on a strip chart. The magnetic field is held to the correct value by a feedback control from one component of the signal. Controls sound an alarm if the chemical ratio exceeds present limits, and many fail-safe controls warn the operator if the ,monitor equipment becomes disabled.
gyroscope will precess in the earth’s gravitational field. The precessional frequency is determined by the ratio of the magnetic moment to the spin and is directly proportional to the magnetic field strength. For protons, this frequency is 4.2577 mc. per kilogauss. The process monitor described here uses proton resonance at a frequency of 30 mc. ; this, therefore, requires that the magnetic field be approximately 7050 gauss. The resonance of the protons is very narrow if all these nuclei are in exactly the same magnetic field. In a solid substance, the adjoining nuclei perturb the field so that a sharp line is rare, but in a low viscosity liquid, the molecules move about so rapidly that molecular neighbors’ effects upon each other are rapidly averaged out. This can permit all like nuclei to resonate together if they are in the same magnetic field. Such is the case of the proton line of water. I n most molecules the magnetic field within the molecule is not equal to the field applied by the magnet but is modified TRANSMITTER COIL RECEIVER COIL
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Theory All nuclei do not produce magnetic resonance signals. T o do so they must have angular momentum (spin) and a magnetic moment. Also, of the isotopes which can be observed with NMR, only a few have the adequate natural abundance and magnetic characteristics which make them useful isotopes for high resolution work. Hydrogen-1 is the most important; fluorine-19, phosphorus-31, and boron-11 are often used. A nucleus which has angular momentum and a magnetic moment may be pictured as a bar magnet spinning about its axis. When it is placed in a magnetic field, it tends to align itself with the field; however, as it has angular momentum, or spin, it will precess about the magnetic field lines just as a top or
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-. ..- . .. - .. . Simplified diagram of high-resolution NMR process monitor shows basic elements
by the local environment of the nuclei. This magnetic field shift inside the molecule, caused by nearby atoms of the same molecule, results in nuclei of the same species resonating at slightly different external magnetic fields. This field shift in proton resonance can be as much as 10 p.p.m. but generally is much less. One useful property of NMR is that resonance intensity is proportional to the number of resonating nuclei in a given portion of a complex molecule. This permits a direct measurement of the ratio of similar nuclei in different parts of the molecule or, if a mixture is being measured, as in this process monitor, it is still a ratio of the number of like nuclei in one part of one molecule to a part or all of another molecule. If the applied magnetic field is swept in a linear manner, the area of a resonance line is proportional to the number of atoms represented by that line. Instrumentation
The basic essentials of usual highresolution NMR equipment are a magnet, a transmitter, a probe containing the sample, a receiver, a sweep to scan the magnetic field, and some sort of indicator such as an oscilloscope or recorder. The most difficult component to construct is the magnet, not only because it is required to deliver a field which is uniform to one part in 10 million or better over the sample but also because it must maintain this exact and uniform field for long periods of time. The instrument described here (see diagram) used a system in which a radiofrequency generator, or transmitter, fed a 30-mc. current into a transmitter coil located in the probe. The probe was in the homogeneous magnetic field (7050 gauss) of the electromagnet, and inside this probe the transmitter coil induced a rotating field of 30 mc. a t the chemical sample so that any protons of this sample could be forced into precession. This liquid sample flowed through the probe in a vertical VOL. 52, NO. 6
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PROCESS C O N T R O L 3-mm. (inside diameter) glass tube. The precessing nuclei induced a voltage into another coil connected to a highgain amplifier and detection system commonly called the receiver. An NMR signal is extremely weak, and great care is required to prevent loss of the signal in noise. The transmitter had crystal control of its frequency and an adjustable output always less than 1 watt (set for maximum NMR signal without saturation of the spin system). The receiver had a gain of about 10 million before the detector; the amplifiers were specially constructed so that the detected signal could be over 100 volts if desired. The unusually high output level reduced the amount of required shielding against noise in the programming circuits to follow. The saw tooth sweep for the magnetic field was generated by a motor-driven 360" potentiometer which rotated once every 6 seconds. Current from the amplified sweep was fed to a pair of coils on the outside of the probe so that the steady magnetic field a t the sample was swept every 6 seconds. The probe, as shown in the magnet gap, had three coils with orthogonal orientation. The receiver coil was located inside the transmitter coil, and the sample flowed inside the receiver coil. The sweep coils were on the outside of the probe. The saw tooth sweep of magnetic field allowed a repetitive analysis of the proton resonances inside the molecule. To measure the ratio of nuclei in each component, the areas of two resonance lines were compared. Automatic gain control of the receiver was used to keep the output of the stronger resonance constant over long periods of time. A probe control also was included so that adjustments of magnetic field homogeneity could be controlled from a distance of about 100 feet from the magnet. The magnet, radio-frequency probe, and receiver preamplifier were located at the process stream, while the rest of the instrument was in a separate control room. Small
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Observable Output of RF Receiver
NMR signals from the radio-frequency receiver show two sweeps of the spectrum here 488
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NMR signals were recorded here after gain reducfion and inversion of larger signal Weaker signal i s upright) stronger signal has been attenuated and inverted
The control and measuring system included the motor-driven sweep potentiometer and, also on the same shaft, eight cams, each operating a microswitch for programming the receiver. The receiver output (lower left) was sampled during three periods of each sweep: once during the resonance of the large signal of one compound in the mixture being monitored, again during a weaker line of a second compound, and finally when there was no NMR resonance. The latter interval was used to establish a zero base for measuring other intensities. The signal was repeated each 6 seconds with the large signal at the end of the sweep; the smaller signal was just ahead of the larger one and had an amplitude of about 2 or 3% of the larger signal. Preceding the smaller signal was the zero output trace used to establish a reference voltage. A slight drift of either frequency or field strength would move the lines outside any time gates of the spectrum, so a simple proton resonance field control was used. The strongest spectrum line was switched so that its leading half was fed into one integrator, the trailing half into another. The difference voltage of the integrators was amplified to run a small? variable-speed motor which could, if necessary, continually vary the electromagnet current to maintain the correct field. Improved methods of locking field and frequency are now available, but the presence of one strong proton resonance permitted use of this simple system. Because one signal in the application was much larger than the other, the stronger line was attenuated to approximately the same value as the weaker one before comparison. During the total time of sweep across the strong line, the receiver was also switched through an attenuator into another integrator. As the weaker line passed, it was switched to a similar integrator without attenuation, The two integrators were fed
INDUSTRIAL AND ENGINEERING CHEMISTRY
to a differential amplifier whose output could be calibrated directly in ratios of the two substances. The two bottom switches, IvIS207 and MS208 (below), connected the large signals to the pair of integrators for magnet field control. Switch MS205 clamped the output to establish zero reference; MS204 connected the attenuated large signal to its integrator; MS203 connected the small signal to its integrator while MS206 removed this attenuation. As an additional check, another cam switch, MS202, inverted one signal so that the attenuated large signal and the small signal could be recorded directly on a fast galvanometer recorder. The monitor recording with fast paper speed is shown (at left). Sormally a much slower paper speed was used, but signal reversal allowed easy separation of the two resonances. The other recorder, with a 24-hour chart, was used as a ratio monitor and could be calibrated directly as a ratio of the two compounds. I n one application, the recorder on this differential amplifier was calibrated for ranges of about 1 to 5%.
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The cam-operated switching sequence was synchronized with the 6-second sweep
Operation. Equipment was calibrated by chemical analysis, but calibrated ratio controls could have been used if required, or a complete spectrum could have been recorded and the ratio measured by area integration. In this instrument the system was checked periodically by a simulated spectrum. The probe could be replaced by an electrostatic coupling unit modulated by holes in a rotating drum. The output, similar to a normal spectrum of a known ratio, was used for calibrating recorders and meters. With some mixtures it would be possible to calibrate by adding a separate, fixed sample in the probe alongside the flow stream. This sample or mixture should have resonances outside the measured spectrum of the mixture in the process stream. Several fail-safe alarm signals were
used. The signal comparator had a limit meter for either too high or too low a ratio which sounded a warning alarm until reset. The integrators which fed the comparator circuit had time constants of about 10 sweeps (1 minute) so that noise fluctuations did not actuate the alarm. Operational failure alarms sounded if the control signal was too large or too small, if field control operated at the limit of its range, if one of several magnet troubles developed, or if other potential malfunctions existed. In many cases, signal loss was sufficient to give operational alarm, but the other circuits helped localize the trouble. If flow stopped the sample remained in the probe, and signals continued to come through; therefore, a nonflow alarm was required. Discussion
There are several problems associated with an NMR instrument. In normal high resolution spectroscopy, the sample tube is spun rapidly to sharpen the lines. Spinning can cause the nuclei in a plane to resonate a t the average of a slightly inhomogeneous magnetic field instead of the scattered field values. Sample spinning is not usually practical in a process monitor because of the continuously flowing sample, and, therefore, it is necessary to have a very good magnet. Any slight mechanical deformation of the magnet leads to a degradation of field homogeneity and, therefore, of resolution. In this equip-
ment, it would have been impossible to separate the small signal from the edges of the large signal. The magnet environment had to be carefully controlled to prevent a change of field shape. Another stream problem occurs because nuclei need several seconds in the magnetic field to polarize; otherwise there is loss of signal amplitude (2, 6). A small reservoir in the magnet field just outside the probe eliminates this problem (see photograph). The inlet flow enters the bottom of the probe through the relaxation delay chamber. The sample, where it passes through the probe, must be contained in an electrical insulator such as glass, ceramic, or a plastic such as Lucite or Teflon. The instrument measures a sample at room temperature, but a Dewar tube would permit either high or low temperatures. Another, more difficult problem occurs if each nucleus spends too short a time in the measuring area inside the probe. If the period of measurement is equal to or shorter than the inverse line width of NMR resonance, each resonance is broadened. This cannot be prevented except by slowing down sample flow. The flow might be stopped momentarily during measurement, but in this instrument a flow rate of a few inchesper minute gave satisfactory results. A rapidly varying flow tate caused some error in output. There have been many advances in high resolution NMR since this instrument was designed, especially in producing magnetic fields. The homo-
geneity of magnets has been improved, and, even more important for process monitor or control, the time stability of the field has been improved more than an order of magnitude. The field and frequency now can be locked together to one part in 100 million or 1 billion. Improved control of field strength makes possible simultaneous readout of several lines and even their continuous measurement. This will increase the speed of gathering information and its accuracy. Field homogeneity stability (the ability of the magnet to keep its homogeneous field) has also been improved so that good resolution can now be maintained indefinitely. Modern techniques which minimize the base line wander of the receiver output permit a simpler, more accurate method of normalizing the zero reference and thereby increase the signal measuring accuracy. Another improvement has been the production of magnets with high resolution capabilities at twice the field strength as that used in the NMR monitor described here. Thus, GO mc. frequency in a 14.1-kilogauss magnet field spreads the spectrum out twice as wide as that of 30 mc. and simplifies the separation of most proton lines. Furthermore, a signal-to-noise enhancement of about 2 to 1 is achieved. This instrument demonstrated that high-resohtion NMR can be used for a process monitor or control, and certainly a modernized version of this instrument could do a superior job. As with most spectroscopic instrumentation, this equipment is not as simple or inexpensive as many older types of control, and it should not be considered as a replacement for such simple equipment. Rather, high-resolution NMR should be used where the ratios are difficult or impossible to determine by ordinary methods or where measurement or control of a ratio must be accomplished rapidly without any effect upon the composition of the compounds in the flow stream. literature Cited (1) Bloch, F., Hansen, W. W., Packard, M. E., Phys. Rev. 69, 127 (1946). (2) Bloom, A. L., Shoolery, J. N., Ibid.,
90, 358 (1953). (3) Pople, J. A., Schneider, W. G., Bernstein, H. J., “High-Resolution Nuclear Magnetic Resonance,” McGraw-Hill, New York, 1959. (4) Purcell, E. M., Torrey, H. C., Pound, R. V., Phys. Rev. 69,37 (1946). (5) Roberts, J. D., “Nuclear Magnetic Resonance,” McGraw-Hill, New York, 1959. . (6) Suryan, G., Proc. Indian Acad. Sci. A33, 107 (1951). RECEIVED for review September 15, 1959 ACCEPTED April 1, 1960
View into magnet g a p shows NMR probe, sample flow tubes, and relaxation delay chamber which provides time for nuclei to polarize
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