electronics

Review Advances in Electronics Prompt a Fresh Look at Continuous (CW) Nuclear Magnetic Resonance (NMR)

Michael I. Newton, Edward A. Breeds and Robert H. Morris *

School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK; [email protected] (M.I.N.); [email protected] (E.A.B.) * Correspondence: [email protected]; Tel.: +44-115-848-3123

Received: 1 September 2017; Accepted: 3 October 2017; Published: 23 October 2017

Abstract: Continuous Wave Nuclear Magnetic Resonance (CW-NMR) was a popular method for sample interrogation at the birth of magnetic resonance but has since been overlooked by most in favor of the now more popular pulsed techniques. CW-NMR requires relatively simple electronics although, for most designs, the execution is critical to the successful implementation and sensitivity of the system. For decades there have been reports in the literature from academic groups showing the potential of magnetic resonance relaxation time measurements in industrial applications such as the production of food and drink. However, the cost, complexity and power consumption of pulsed techniques have largely consigned these to the literature. Advances in electronics and developments in permanent magnet technology now require a fresh look at CW-NMR to see if it is capable of providing cost effective industrial solutions. In this article, we review the electronics that are needed to undertake a continuous wave NMR experiment starting with early designs and journeying through the literature to understand the basic designs and limitations. We then review the more recent developments in this area and present an outlook for future work in the hope that more of the scientific community will take a fresh look at CW-NMR as a viable and powerful low-cost measurement technique.

Keywords: continuous wave nuclear magnetic resonance; CW-NMR; spectrometer

1. Basic Principles of Continuous Wave Nuclear Magnetic Resonance Nuclear magnetic resonance (NMR) is an extremely powerful tool, capable of non-invasively providing information about molecular environments and their fundamental physical properties. Since the birth of the nuclear magnetic resonance experiment in the 1930s [1,2], significant advances in understanding and utilizing the technique [3–5], alongside an ever increasing number of applications [6–9], have led NMR to the forefront of analytical techniques used in physics, chemistry and medicine. Two of the most notable contemporary applications of magnetic resonance are Magnetic Resonance Imaging (MRI) and Chemical Shift NMR (often referred to simply as NMR). NMR uses the response of the intrinsic nuclear magnetic moment of certain nuclei to externally applied magnetic fields and the application of appropriate (RF) signals to probe their local environment. Nowadays, more common is the so called Pulsed NMR experiment—these nuclear magnetic moments can, from a classical mechanics perspective, be considered as microscopic bar magnets that align themselves with a strong applied magnetic field (along an arbitrary z-axis). RF radiation at a frequency ω is then applied, to satisfy the so-called Larmor condition [10] (see Equation (1)), which

Electronics 2017, 6, 89; doi:10.3390/electronics6040089 www.mdpi.com/journal/electronics Electronics 2017, 6, 89 2 of 21 tips these magnetic moments such that they are normal to the original field (and the spins lie in the x-y plane). ω = γB0 (1) In this expression, ω is the frequency of precession of a given nuclei within a magnetic field of magnitude B0. The gyromagnetic ratio γ is a constant of proportionality characteristic of the nuclei (42.58 MHz T−1 for the proton). The principle of reciprocity suggests that applying energy at this same frequency will yield optimum manipulation of the magnetic moments. For most pulsed experiments utilizing protons, this is in the radio frequency range and so this is often termed an RF pulse. The tipped moments then rotate in the x-y plane (a motion termed precession) about the axis of the external magnetic field at a rate dependent on their local field strength. The net magnetization vector has sufficient magnitude that electromagnetic induction in a coil surrounding them, after amplification, yields a detectable signal. Within this signal are components for each frequency of precession and hence information about the local magnetic fields. In Chemical Shift Spectroscopy, these provide molecular information, in MRI they encode spatial information. Both of these experiments are grouped under the wider title of Fourier transform magnetic resonance (FT-MR). A large number of commercial low-cost pulsed NMR systems are available, although for many applications these are still considerably more expensive than is viable for many sensor applications. In recent years, a number of ultra-low-cost systems have been discussed in the literature but, to date, none have reached the stage of development which allows them to be commercially deployed. Continuous wave magnetic resonance on the other hand, more commonly called Continuous Wave Nuclear Magnetic Resonance (CW-NMR), has largely been neglected for the past half century. Despite being the forerunner of the pulsed experiment, the technology of the time provided a comparatively poor signal, requiring significant effort in set up and tuning, ultimately leading to the demise of CW-NMR for all but a small handful of applications. In contrast to the FT-MR experiment, the CW-NMR experiment is simpler: sweeping the sample through the Larmor condition with a time varying magnetic field or frequency of irradiation, while monitoring the amount of energy which it absorbs. Investigating the absorption of the RF energy by the ensemble of magnetic moments provides information about their quantity and environment [11]. CW-NMR is today found in many undergraduate physics laboratories and is seen by many as a useful teaching aid in understanding magnetic resonance, given its comparative simplicity. Almost all such experiments however still employ oscilloscope detection, despite the prevalence of fast data capture hardware, capable of digitizing even the raw RF signals with minimal cost. In this article, we present a review of the wide array of electronic hardware that has been used to undertake the continuous wave NMR experiment throughout the existence of the technique, followed by a discussion on the quantification of material properties. The final section considers how modern electronics are allowing the more basic of the NMR techniques to be used in a quantitative sense, in the hope that more scientists will consider CW-NMR for low-cost automated measurements of material properties.

2. Humble Beginnings Although the first successful magnetic resonance absorption experiments reported by Purcell, Torry and Pound in 1946 [3] utilized a bridge circuit, which will be discussed in the next section; the most basic CW-NMR experiment was reported in 1949 by Rollins [12] and is shown in Figure1. A is used to supply RF to a tuned circuit through a resistor, resulting in a constant current signal, and the magnetic field in which the sample sits is varied using so-called sweep coils. During this process, the of the RF is monitored (after it is amplified and rectified). As the field of the sample approaches resonance, more energy is absorbed and hence the amplitude of the RF signal becomes ever lower until the Larmor condition is met. The signal then increases back to equilibrium as the field continues to change. Electronics 2017, 6, 89 3 of 21 ElectronicsElectronics 2017 2017, ,6 6, ,89 89 33 of of 21 21

FigureFigure 1.1. RollinsRollins basicbasic ContinuousContinuous WaveWave Nuclear NuclearNuclear Magnetic MagneticMagnetic Resonanceexperiment. Resonanceexperiment.Resonanceexperiment.

TheTheThe limiting limitinglimiting factor factorfactor in in this,in this,this, and andand any suchanyany such system,such systsyst relatesem,em, relatesrelates to the order toto thethe of order magnitudeorder ofof magnitudemagnitude of the amplitude ofof thethe modulationamplitudeamplitude modulationmodulation due to absorption. duedue toto abso Thisabsorption.rption. was calculated ThisThis waswas for calculatedcalculated protons in forfor water protonsprotons at 21.3 inin water MHzwater byatat 21.3 Andrew21.3 MHzMHz [13 byby] toAndrewAndrew be less [13] than[13] toto 1%, bebe which lessless thanthan represents 1%,1%, whichwhich the best-caserepresentsrepresents scenario. thethe best-casebest-case This means scenario.scenario. that ThisThis significant meansmeans amplification thatthat significantsignificant is requiredamplificationamplification and, forisis requiredrequired improved and,and, signal forfor improved toimproved noise ratio, signalsignal the toto original noisenoise ratio,ratio, class the ofthe circuit originaloriginal utilizing classclass ofof bridges circuitcircuit isutilizingutilizing in fact preferable.bridgesbridges isis in Inin fact suchfact preferable.preferable. a setup, only InIn such thesuch change aa setup,setup, in signalononlyly thethe due changechange to the absorptioninin signalsignal duedue isamplified, toto thethe absorptionabsorption providing isis aamplified,amplified, far higher providingproviding dynamic range aa farfar higher thanhigher in dynamic anydynamic amplifier rangerange setup. ththanan Examplesinin anyany amplifieramplifier of bridge setup.setup. circuits ExamplesExamples are discussed ofof bridgebridge in thecircuitscircuits following areare discusseddiscussed section. inin thethe followingfollowing section.section.

3.3.3. BridgeBridge CircuitsCircuits AsAsAs alludedalluded tototo inin thethe previousprevious section,section,section, aaa popularpopular meansmeans ofofof monitoringmonitoring RF RFRF absorptionabsorptionabsorption is isis thethethe useuseuse ofof aaa bridge.bridge.bridge. This ThisThis circuit circuitcircuit design designdesign utilizes utilizesutilizes at at leastat leastleast two twotwo so-called so-calledso-called arms, arms,arms, which, which,which, in the inin absence thethe absenceabsence of a sample, ofof aa sample,sample, have similarhavehave similarsimilar impedance. impedance.impedance. When aWhenWhen sample aa sample issample introduced, isis intrintroduced, theoduced, relative thethe impedance relativerelative impedanceimpedance changes at changeschanges the frequency atat thethe offrequencyfrequency absorption ofof absorption andabsorption a voltage andand appears aa voltagevoltage at the appearsappears output atat of thethe the outputoutput bridge. ofof As thethe a result, bridge.bridge. when AsAs a offa result,result, resonance, whenwhen the offoff amplifierresonance,resonance, only thethe needsamplifieramplifier to amplify onlyonly needsneeds noise, toto amplify notamplify a maximal noise,noise, not not signal aa maximalmaximal as in the signal signal example asas in in of thethe Figure exampleexample1, and ofof henceFigureFigure one1,1, andand can hencehence use far oneone more cancan sensitive useuse farfar more electronics.more sensitivesensitive Off electron resonance,electronics.ics. the OffOff output resonance,resonance, of the thethe bridge outputoutput is noise ofof thethe rather bridgebridge than isis signal.noisenoise rather rather When than than the signal. magneticsignal. When When field the the is magnetic magnetic then swept field field through is is then then resonance,swept swept through through a voltage resonance, resonance, becomes a a voltage voltage present becomes becomes at the output,presentpresent which atat thethe output,isoutput, fed to which awhich sensitive isis fedfed preamplifier. toto aa sensitivesensitive Such preamplifier.preamplifier. circuits are SuchSuch also circuits verycircuits popular areare alsoalso in very magnetometersvery popularpopular inin wheremagnetometersmagnetometers the resonance wherewhere of the athe known resonanceresonance sample ofof isaa known usedknown to samp determinesamplele isis usedused the magnetic toto determinedetermine field thethe in which magneticmagnetic the samplefieldfield inin sitswhichwhich [14 ], thethe with samplesample a schematic sitssits [14],[14], for withwith such aa aschematicschematic circuit shown forfor suchsuch in Figure aa circuitcircuit2. It shownshown should inin be FigureFigure noted 2. that2. ItIt should itshould is essential bebe notednoted to undertakethatthat itit isis essentialessential careful balancing toto undertakeundertake of any carefulcareful bridge balancingbalancing circuit [ 15 ofof]. anyany That bridgebridge is to say circuitcircuit that [15]. if[15]. the ThatThat two is armsis toto saysay of the thatthat bridge, ifif thethe offtwotwo resonance, armsarms ofof thethe are bridge,bridge, not sufficiently offoff resonance,resonance, similar areare in not termsnot sufficientlysufficiently of their impedance, similarsimilar inin terms theterms output ofof theirtheir will impedance,impedance, be RF leakage thethe whichoutputoutput may willwill be bebe sufficient RFRF leakageleakage to which overloadwhich maymay a sensitivebebe sufficientsufficient . toto overloadoverload aa sensitivesensitive detector.detector.

FigureFigureFigure 2. 2. An AnAn example example example bridge bridge bridge circuit circuit circuit used used in in used an an early early in magnetometer anmagnetometer early magnetometer to to determine determine to magnetic magnetic determine field field magnetic strength. strength. field strength. InIn mostmost cases,cases, bridgebridge balancingbalancing isis aa complexcomplex andand time-consumingtime-consuming processprocess thatthat requiresrequires significantsignificant skillskill andand patiencepatience onon thethe partpart ofof thethe experimentalist.experimentalist. AA possiblepossible solutionsolution toto thisthis waswas

Electronics 2017, 6, 89 4 of 21

Electronics 2017, 6, 89 4 of 21 In most cases, bridge balancing is a complex and time-consuming process that requires significant suggestedskill and patiencein 1957, where on the voltage part of controlled the experimentalist. capacitors were A possible employed solution to allow to this for wasautomatic suggested bridge in balancing1957, where [16]. voltage A small controlled oscillating capacitors voltage were with employedhigh frequency to allow is used for automatic to check for bridge balance, balancing which [16 is]. thenA small automatically oscillating voltage corrected with with high minimal frequency deteriora is used totion check of forthe balance,NMR signal which (see is then Figure automatically 3). This representscorrected withan elegant minimal solution deterioration to the issue of theof ba NMRlance signal which(see has Figurenot been3). widely This represents adopted, despite an elegant the easesolution of operation. to the issue of balance which has not been widely adopted, despite the ease of operation.

Figure 3. An example of automatic bridge circuit balancing (Correction voltage applied through A). Figure 3. An example of automatic bridge circuit balancing (Correction voltage applied through A). The output signal from a bridge circuit is however very small and often buried within the noise floor. TheTo combat output signalthis, a fromrectifier a bridge and lock-in circuit isamplifier however are very employed, small and the often fundamental buried within principles the noise of whichfloor. Towill combat be discussed this, a rectifierhere, with and the lock-in reader amplifier referred areto an employed, excellent thedescription fundamental for further principles detail of [17].which For will very be weak discussed signals here, that with vary the with reader a well-known referred to anperiodicity, excellent descriptionand for which for the further bandwidth detail [17 of]. traditionalFor very weak amplifiers signals would that lead vary to with signal a well-known to noise ratios periodicity, less than 1, and lock-in for whichamplification the bandwidth allows for of accuratetraditional extraction. amplifiers Lock-in would amplifiers lead to signal are based to noise around ratios the less principles than 1, lock-in of a phase amplification based detector, allows whichfor accurate utilizes extraction. a reference Lock-in signal amplifierswith similar are frequency based around to (or the sometimes principles twice of a phasethat of) based the signal detector, of interest.which utilizes The output a reference of the phase signal sensitive with similar detector frequency is the sum to (or and sometimes difference twice of the that two of) input the signalsignals. of Byinterest. filtering The out output the sum of the component phase sensitive with a detector low pass is thefilter, sum only and the difference difference of is the output, two input which, signals. for casesBy filtering of the outsame the frequency sum component input and with reference, a low pass leads filter, to a only DC thevoltage difference proportional is output, to which,the input for voltage.cases of This the samevoltage frequency is then inputfed to anda traditional reference, amplifier leads to awhich DC voltage now only proportional has the variations to the input of interestvoltage. to This amplify voltage and is hence then fed can to do a traditionalso with a fa amplifierr greater whichSNR output. now only In works has the such variations as Bloembergen of interest andto amplify other utilizing and hence bridges, can do the so with a far greatercoil voltage SNR is output. used as Inthe works lock-in such reference as Bloembergen [18], although and thisother can utilizing also be bridges, achieved the by modulation applying coilan additional voltage is usedaudio as frequency the lock-in to reference the sweep, [18], which although offers this furthercan also sensitivity be achieved to the by reference. applying an additional audio frequency to the sweep, which offers further sensitivity to the reference. 4. Double Coil Circuits 4. Double Coil Circuits In the systems discussed thus far, the amount of energy absorbed by the sample has been determinedIn the by systems measuring discussed the absence thus far, or theimbalance amount of ofan energyRF signal absorbed on resonance. by the A sample less frequently has been useddetermined setup, sees by measuringthe use of two the absencecoils, one or of imbalance which delivers of an RFRF signalenergy on to resonance.the sample Ain less one frequently direction whileused setup,the other sees thesubsequently use of two coils,measures one ofthe which resulting delivers signal RF energyfrom precession to the sample in inan one orthogonal direction direction.while the otherWith subsequentlyaccurate alignment, measures the the incident resulting RF signalcan be from eliminated precession from in anthe orthogonal receive electronics direction. chain,With accurate allowing alignment, for very sensitive the incident preamplifiers RF can beeliminated and minimal from noise the receive[11,19]. electronicsThe challenge chain, with allowing such afor setup, very as sensitive with balancing preamplifiers the bridges and minimal of the prev noiseious [11 ,experiments,19]. The challenge is the with requirement such a setup, of ensuring as with thatbalancing there is the minimal bridges leakage of the previous from the experiments, first coil into is the the second. requirement The typical of ensuring method that of thereachieving is minimal such aleakage condition from is to the utilize first coil a metallized into the second. paddle The[11], typicalas shown method in Figure of achieving 4, to steer such the aflux condition lines of isthe to transmitutilize a metallizedsolenoid to paddle one side [11 or], asthe shown other, in thus Figure allowing4, to steer almost the fluxcomplete lines of isolation the transmit of the solenoid two coils to (secondone side coil or thenot other,shown). thus allowing almost complete isolation of the two coils (second coil not shown).

Electronics 2017, 6, 89 5 of 21 Electronics 2017, 6, 89 5 of 21 Electronics 2017, 6, 89 5 of 21

Figure 4. Flux steering method. (reproduced (reproduced with permission from [11]. [11]. Copyright Copyright American Physical Figure 4. Flux steering method. (reproduced with permission from [11]. Copyright American Physical Society, 1946)1946) ((aa)) UnperturbedUnperturbed magneticmagnetic fluxflux generatedgenerated byby aa solenoid;solenoid; aa metallized paddlepaddle being used Society, 1946) (a) Unperturbed magnetic flux generated by a solenoid; a metallized paddle being used to steer fluxflux ((b)) downwardsdownwards oror ((cc)) upwardsupwards inin thethe samesame coil.coil. TheThe receivereceive coilcoil isis notnot shown.shown. to steer flux (b) downwards or (c) upwards in the same coil. The receive coil is not shown. In some laboratory experiments, such as that shown in Figure 5, this is further aided by the use In some laboratory experiments, such as that shown in Figure5, this is further aided by the use of Inof some a waveguide laboratory and experiments, physical separation such as thatof the show coilsn inby Figure some distance 5, this is [20].further aided by the use of a waveguidea waveguide and and physical physical separation separation of the of thecoils coils by some by some distance distance [20]. [20 ].

Figure 5. Further coil isolation using a waveguide and physical separation. Figure 5. Further coil isolation using a waveguide and physical separation. Figure 5. Further coil isolation using a waveguide and physical separation. Although the so-called transmit and receive chains (referring to the path leading to the first coil Althoughdelivering the the so-called RF and thattransmit leading and away receive from chains the se (referringcond coil todetecting the path the leading NMR tosignal, the first respectively) coil Although the so-called transmit and receive chains (referring to the path leading to the first coil deliveringare normally the RF and isolated that leading from each away other, from a the bridge second may coil be detecting introduced the between NMR signal, the two respectively) coils [19] which delivering the RF and that leading away from the second coil detecting the NMR signal, respectively) are normallycan be usedisolated to suppress from each any other, leakage. a bridge This maymay befurther introduced improve between the signal the twoto noise coils ratio. [19] which can beare used normally to suppress isolated any from leakage. each This other, may a bridge further may improve be introduced the signal between to noise theratio. two coils [19] which can be used to suppress any leakage. This may further improve the signal to noise ratio. 5. Non-Isolated Oscillator Circuits 5. Non-Isolated Oscillator Circuits 5. Non-IsolatedThus far, our Oscillator discussion Circuits has been limited to RF sources that are essentially isolated from the Thus far, our discussion has been limited to RF sources that are essentially isolated from the resonantThus portions far, our of discussion the circuits. has That been is limited to say, to as RF the sources sample that is swept are essentially through resonance, isolated from the theRF resonant portions of the circuits. That is to say, as the sample is swept through resonance, the RF resonantsource remains portions unchanged. of the circuits. In the next That sections is to say, we as w theill consider sample isa class swept of throughcircuit where resonance, the RF thesource RF source remains unchanged. In the next sections we will consider a class of circuit where the RF source sourceis in fact remains resonant unchanged. with the sample In the nextand sectionsvaries in we some will way consider as the a sample class of is circuit swept where through the resonance. RF source is in fact resonant with the sample and varies in some way as the sample is swept through resonance. isThis in factallows resonant us to move with theaway sample from the and stringent varies in re somequirements way as thefor balancing sample is sweptbridges. through Oscillator resonance. driven This allows us to move away from the stringent requirements for balancing bridges. Oscillator driven Thissystems allows are usmore to move convenient away fromin many the stringentapplications, requirements particularly for balancingmagnetometers bridges. where Oscillator it is only driven the systems are more convenient in many applications, particularly magnetometers where it is only the systemsamplitude are of more the absorption convenient sign in manyal and applications, not its shape particularly or width (known magnetometers as the linewidth) where it isthat only is amplitude of the absorption signal and not its shape or width (known as the linewidth) that is theimportant. amplitude We ofwill the first absorption consider signalcircuits and utilizing not its a shape magnetic or width field (knownsweep, which as the we linewidth) have primarily that is important. We will first consider circuits utilizing a magnetic field sweep, which we have primarily important.looked at so Wefar, willfollowed first considerby circuits circuits for which utilizing the field a magneticremains unchanged field sweep, whilst which the wefrequency have primarily is swept. looked at so far, followed by circuits for which the field remains unchanged whilst the frequency is swept. looked at so far, followed by circuits for which the field remains unchanged whilst the frequency 5.1. Oscillator Circuits Using Magnetic Field Sweep is swept. 5.1. Oscillator Circuits Using Magnetic Field Sweep In this section we will review two types of oscillators which are used when the magnetic field of In5.1.the this sample Oscillator section is weswept Circuits will whilst review Using beingMagnetic two typesdriven Field of by oscillators Sweep an oscillation which at are a continuous used when frequency. the magnetic The field first of class of the samplesuch In anis thisswept oscillator section whilst is we known being will reviewdriven as the marginalby two an types oscill oscillator. ofation oscillators at a continuous which are frequency. used when The the first magnetic class of field of such anthe oscillator sample isis sweptknown whilst as the being marginal driven oscillator. by an oscillation at a continuous frequency. The first class of such5.1.1. anMarginal oscillator Oscillators is known as the marginal oscillator. 5.1.1. Marginal Oscillators One of the most frequently employed oscillator type circuits for use in continuous wave NMR 5.1.1. Marginal Oscillators Oneis the of marginalthe most frequentlyoscillator. Theemployed basis of oscillator this system type is circuits a tank forcircuit use incomprising continuous a samplewave NMR coil and a is the capacitor.marginalOne of oscillator.This the is most then The frequently driven basis with ofemployed this energy system from oscillator is aa vatanklve type circuitor transistor circuits comprising for circuit use ina which sample continuous is justcoil sufficient waveand a NMR to capacitor.issustain the This marginal oscillation. is then oscillator.driven Any with subsequent The energy basis fromincrease of this a va systeminlve loading, or transistor is a as tank caused circuit by which comprising sweeping is just through asufficient sample resonance, coilto and sustainresults oscillation. in a reduction Any subsequent in amplitude increase which in loading,can be subsequently as caused by detected sweeping with through methods resonance, such as those resultsthat in a we reduction have already in amplitude considered. which can be subsequently detected with methods such as those that we have already considered.

Electronics 2017, 6, 89 6 of 21 a capacitor. This is then driven with energy from a valve or transistor circuit which is just sufficient to sustainElectronics oscillation. 2017, 6, 89 Any subsequent increase in loading, as caused by sweeping through resonance,6 of 21 resultsElectronics in 2017 a reduction, 6, 89 in amplitude which can be subsequently detected with methods such as those6 of 21 that weFigure have 6 already shows considered.a possible signal obtained during a sweep of the magnetic field, showing Figure 6 shows a possible signal obtained during a sweep of the magnetic field, showing amplitudeFigure modulation6 shows a possible caused signal by the obtained change during in loading. a sweep It should of the magnetic be noted field,that in showing this example, amplitude the caused by the change in loading. It should be noted that in this example, the modulationRF energy is causedof a significantly by the change lower in frequency loading. It than should would be noted be expected that in in this a real example, experiment the RF and energy the RF energy is of a significantly lower frequency than would be expected in a real experiment and the isdepth of a of significantly the dip is significantly lower frequency larger. than As a would result, be diode expected detection in a realis normally experiment required and and the depthis found of depth of the dip is significantly larger. As a result, diode detection is normally required and is found thein almost dip is significantlyall receiver circuits. larger. As After a result, it is dioderectified, detection the signal is normally is normally required passed and isthrough found inan almost audio in almost all receiver circuits. After it is rectified, the signal is normally passed through an audio allfrequency receiver or circuits. lock-inAfter amplifier. it is rectified, the signal is normally passed through an audio frequency or frequency or lock-in amplifier. lock-in amplifier.

Figure 6. An example of amplitude modulation caused by changes in loading. Note that the width of Figure 6. An example of amplitude modulation caused by changes in loading. Note that the width of the dip isis greatlygreatly exaggeratedexaggerated forfor clarity.clarity. the dip is greatly exaggerated for clarity. Unlike the bridge circuits, where a change in the resonance condition must be accounted for by UnlikeUnlike thethe bridgebridge circuits,circuits, wherewhere aa changechange inin thethe resonanceresonance conditioncondition mustmust bebe accountedaccounted forfor byby retuning the RF source, the marginal oscillator is itself part of the resonant circuit and thus tracks the retuningretuning thethe RF source, the the marginal marginal oscillator oscillator is is itse itselflf part part of of the the resonant resonant circuit circuit and and thus thus tracks tracks the resonance. This leads to the significant advantage that the detected signal is purely absorption, thanks theresonance. resonance. This This leads leads to the to significant the significant advantage advantage that the that detected the detected signal signalis purely is purelyabsorption, absorption, thanks to the inherent feedback. Any dispersive component of susceptibility produces slight frequency thanksto the toinherent the inherent feedback. feedback. Any Anydispersive dispersive componen componentt of ofsusceptibility susceptibility produces produces slight slight frequencyfrequency modulation of the oscillator, which is not rectified in the detection stage. The classic paper describing modulationmodulation ofof thethe oscillator,oscillator, whichwhich isis notnot rectifiedrectifiedin inthe the detectiondetection stage.stage. TheThe classicclassic paperpaper describingdescribing the bench mark valve based marginal oscillator is by Pound and Knight [21], shown in Figure 7. thethe benchbench markmark valvevalve basedbased marginalmarginal oscillator oscillator is is by by Pound Pound and and Knight Knight [ 21[21],], shown shown in in Figure Figure7 .7.

Figure 7. The classic valve based marginal oscillator. (reproduced with permission from [21]. FigureFigure 7.7. The classic valvevalve basedbased marginalmarginal oscillator.oscillator. (reproduced with permission from [[21].21]. Copyright AIP, 1950). CopyrightCopyright AIP,AIP, 1950). 1950). Some ten years later, with the increasing availability of transistorized electronics, Donnally and Some ten years later, with the increasing availability of transistorized electronics, Donnally and Saunders [22] published a greatly simplified version based around a 2N393 PNP Germanium Saunders [22] published a greatly simplified version based around a 2N393 PNP Germanium transistor. Although the SNR is about half that of the Pound circuit shown in Figure 7, it exhibits very transistor. Although the SNR is about half that of the Pound circuit shown in Figure 7, it exhibits very low power consumption and does not suffer from the problems of microphonics (conversion of low power consumption and does not suffer from the problems of microphonics (conversion of mechanical movement to noise) presented by the valve circuits. In Figure 8, the Donnally and mechanical movement to noise) presented by the valve circuits. In Figure 8, the Donnally and Saunders marginal oscillator is shown, based on a tank circuit feeding into the base of the Germanium Saunders marginal oscillator is shown, based on a tank circuit feeding into the base of the Germanium

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Some ten years later, with the increasing availability of transistorized electronics, Donnally and Saunders [22] published a greatly simplified version based around a 2N393 PNP Germanium transistor. Although the SNR is about half that of the Pound circuit shown in Figure7, it exhibits very low power consumption and does not suffer from the problems of microphonics (conversion of mechanical movementElectronics 2017 to noise), 6, 89 presented by the valve circuits. In Figure8, the Donnally and Saunders marginal7 of 21 oscillator is shown, based on a tank circuit feeding into the base of the Germanium transistor, the outputtransistor, of which the output passes of through which apasses diode through rectifier a and diode narrow rectifier bandwidth and narrow audio bandwidth filter with audio a cut filter off atwith twice a cut the off sweep at twice rate the of thesweep magnetic rate of fieldthe magnet modulationic field coils. modulation The paper coils. also Theprovides paper also an provides audio amplifieran audio circuit amplifier which circuit is of which standard is of design.standard Although design. Although the presented the presented work is basedwork is upon based swept upon magneticswept magnetic fields, the fields, authors the state authors thatC state1 and that C2 can C1 beand substituted C2 can be with substituted voltage variablewith voltage capacitors variable to allowcapacitors for a variable to allow oscillator for a variable sweep. oscillator sweep.

FigureFigure 8. 8.The The Donnally Donnally Saunders Saunders marginal marginal oscillator. oscillator. (reproduced(reproduced withwithpermission permissionfrom from [ 22[22].]. CopyrightCopyright AIP, AIP, 1960). 1960).

TheThe early early circuits circuits operated operated successfully successfully thanks thanks to to a a number number of of transistor transistor parameters parameters that that are are undesirableundesirable for for many many modern modern designs designs (such (such as as those thos thate that limit limit maximum maximum frequency frequency of of operation operation in in amplifieramplifier circuits). circuits). As As transistor transistor technology technology has has continued continued to to improve, improve, the the availability availability of of suitable suitable transistorstransistors became became challenging. challenging. InIn a thesis by by Frank Frank Willingham Willingham [23], [23], this this issue issue was was addressed addressed by byreplacing replacing the the Germanium Germanium transistor transistor of of the the Donnally Sanders circuit withwith aa pairpair of of Field Field Effect Effect TransistorsTransistors (FETs). (FETs). As As well well as as substituting substituting components components for for what what were were then then state state of of the the art, art, the the circuit circuit waswas also also upgraded upgraded for for an an improved improved source source following following the the replacement replacement of of the the traditional traditional resistor resistor with with a seconda second FET. FET. This This provides provides greatly greatly enhanced enhanced source source following following and and enhanced enhanced impedance impedance matching, matching, whichwhich is is of of greatgreat benefitbenefit in in a a circuit circuit where where load load mism mismatchatch is largely is largely responsible responsible for the for detected the detected signal. signal.An Operational An Operational Amplifier Amplifier based based audio audio amplifier amplifier is also is presented, also presented, which which is of standard is of standard design. design. Lock- Lock-inin detection detection is also is also used used in this in this work, work, with with one one sweep sweep coil coil used used for for sweeping sweeping the the resonance resonance of ofthe thesample, sample, whilst whilst a asecond second applies applies a a small, small, higher higher frequency oscillation,oscillation, whichwhich isis fedfed to to the the phase phase sensitivesensitive detector. detector.

5.1.2.5.1.2. Non-Marginal Non-Marginal Oscillators Oscillators AroundAround the the same same time time that that Donnally Donnally and and Sanders Sanders were were updating updating the the Pound Pound circuit, circuit, Robinson Robinson publishedpublished a papera paper [24 [24]] describing describing the the disadvantages disadvantages of marginal of marginal oscillators. oscillators. He suggests He suggests that therethat there are threeare three drawbacks: drawbacks:

“Firstly,“Firstly, they they are are less less sensitive; sensitive; secondly, secondly, they they are are difficult difficult to to adjust adjust at at levels levels below below about about 2020 mV; mV; and and finally finally they they cannot cannot be usedbe used with with circuits circuits of a low of inductancea low inductance to capacitance to capacitance ratio. Ifratio. the shunt If the impedanceshunt impedance of the tunedof the circuittuned circuit is low, is not low, only not is only thenoise is the figurenoise figure impaired impaired but alsobut thealso circuit the circuit may failmay to fail oscillate to oscillate at all.” at all.” He provided an alternative which has become known as the Robinson oscillator [24]. The primary difference between a marginal oscillator and a Robinson oscillator is the feedback loop. Instead of directly feeding back the signal through a resistor, it is fed back through a limiter thus returning a square wave current back to the tank circuit. The construction of a tank circuit is such that it will act as a filter to select the fundamental of the square wave as shown schematically in Figure 9. This ensures that the only non-linearity of the circuit occurs in the limiter, allowing for better prediction and control of the overall oscillation. In other words, the Robinson oscillator is a non- marginal oscillator.

Electronics 2017, 6, 89 8 of 21

He provided an alternative which has become known as the Robinson oscillator [24]. The primary difference between a marginal oscillator and a Robinson oscillator is the feedback loop. Instead of directly feeding back the signal through a resistor, it is fed back through a limiter thus returning a square wave current back to the tank circuit. The construction of a tank circuit is such that it will act as a filter to select the fundamental of the square wave as shown schematically in Figure9. This ensures that the only non-linearity of the circuit occurs in the limiter, allowing for better prediction and controlElectronics of 2017 the, 6 overall, 89 oscillation. In other words, the Robinson oscillator is a non-marginal oscillator.8 of 21 Electronics 2017, 6, 89 8 of 21

(a) (b) (a) (b) FigureFigure 9.9. ((aa)) LimitedLimited self-oscillator;self-oscillator; ((bb)) IdealIdeal characteristicscharacteristics ofof thethe limiter.limiter. Figure 9. (a) Limited self-oscillator; (b) Ideal characteristics of the limiter. Although the original design [25] utilized valves, an updated transistorized version was Although the original design [25] utilized valves, an updated transistorized version was published publishedAlthough in 1965 the [26]. original design [25] utilized valves, an updated transistorized version was in 1965 [26]. publishedFaulkner in 1965 and [26]. Holman however, in a publication two years later [27], claimed that a large number Faulkner and Holman however, in a publication two years later [27], claimed that a large number of transistorizedFaulkner and Robinson Holman however,oscillators in that a publication had previously two years been later published [27], claimed were in that fact a not large true number to the of transistorized Robinson oscillators that had previously been published were in fact not true to the offunctionality transistorized of the Robinson original. oscillators They found, that in had fact, previously that even been that published bywere Robinson in fact not himself true toin thethe functionality of the original. They found, in fact, that even that published by Robinson himself in the functionality1965 paper didof the not original. meet theThey original found, infeedback fact, th atcriteria. even that Following published discussions by Robinson with himself Robinson, in the 1965 paper did not meet the original feedback criteria. Following discussions with Robinson, Faulkner 1965Faulkner paper and did Holman not meet produced the original a transistor feedback version criteria. of a true Following Robinson discussions oscillator, shownwith Robinson, in Figure and Holman produced a transistor version of a true Robinson oscillator, shown in Figure 10. By way Faulkner10. By way and of demonstration,Holman produced they a used transistor their circuit version as ofa magnetometer a true Robinson with osci a llator,rubber shown sample in material Figure of demonstration, they used their circuit as a magnetometer with a rubber sample material up to 10.up Byto away frequency of demonstration, of 30 MHz. they used their circuit as a magnetometer with a rubber sample material aup frequency to a frequency of 30 MHz. of 30 MHz.

Figure 10. A true transistorized Robinson oscillator. FigureFigure 10.10. A truetrue transistorizedtransistorized RobinsonRobinson oscillator.oscillator. An alternative strategy to the use of discrete transistors was described by Deschamps, Vaissiére and AnSullivan alternative [28], strategyutilizing to the the CA3102use of discrete chip thtransistorsat has two was independent described by differentialDeschamps, amplifiers Vaissiére and(although Sullivan only [28], the secondutilizing is usedthe CA3102differentially chip hethre)at withhas twoassociated independent constant differential current transistors amplifiers on (althougha common only monolithic the second substrate. is used differentially This arrangement here) with (shown associated in Figure constant 11) currentallows transistorsfor increased on abandwidth common andmonolithic input impedance, substrate. givingThis arrangement greater stability (shown of measurement in Figure 11)and allows a significant for increased increase bandwidthin whilst and utilizing input impedance, a single integrated giving greater circuit. stability of measurement and a significant increase in gain whilst utilizing a single integrated circuit.

Electronics 2017, 6, 89 9 of 21

An alternative strategy to the use of discrete transistors was described by Deschamps, Vaissiére and Sullivan [28], utilizing the CA3102 chip that has two independent differential amplifiers (although only the second is used differentially here) with associated constant current transistors on a common monolithic substrate. This arrangement (shown in Figure 11) allows for increased bandwidth and input impedance, giving greater stability of measurement and a significant increase in gain whilst Electronicsutilizing 2017, 6 a, 89 single integrated circuit. 9 of 21

FigureFigure 11. Non-marginal 11. Non-marginal oscillation oscillation utilizing the the CA3102 CA3102 chip. chip. (reproduced (reproduced with permission with permission from [28]. from [28]. CopyrightCopyright AIP,AIP, 1977). 1977).

SomeSome years years later, later, in in 1990, 1990, a MOSFETMOSFET version version of a trueof a Robinsontrue Robinson oscillator oscillator was reported was by reported Wilson by Wilsonand and Vallabhan Vallabhan [29]. [29]. The useThe of use MOSFETs of MOSFETs allows allo for significantws for significant reduction reduction in Q-factor in loading Q-factor of the loading of thetank tank circuit, circuit, giving giving a higher a higher dynamic dynamic range forrange the NMRfor the signal NMR since signal the shunt since impedance the shunt of impedance the tank of the tankcircuit circuit is significantly is significantly lower lower than the than input the impedanceinput impedance of the MOSFET. of the MOSFET. They also They reduce also1/ freducenoise 1/ and, thanks to their good transconductance, can be operated at much lower RF levels. noise and, thanks to their good transconductance, can be operated at much lower RF levels. 5.2. Oscillator Circuits Using Frequency Sweep 5.2. Oscillator Circuits Using Frequency Sweep The second type of oscillator, where the magnetic field is constant whilst the sample is driven Thethrough second resonance type of by oscillator, changing the where RF frequency, the magnetic is used field extensively is constant for magnetometer whilst the sample applications. is driven throughThis resonance allows for smallerby changing devices the (as RF there frequency, are no sweep is used coils required)extensively and explorationfor magnetometer of a greater applications. range This allowsof fields for than smaller can be devices achieved (as by retuningthere are field no sweepsweep oscillators. coils required) In a 1951 and paper exploration by Knoebel of [a30 greater], a transitron oscillator is used [31] that utilizes a minimal number of components (see Figure 12) range of fields than can be achieved by retuning field sweep oscillators. In a 1951 paper by Knoebel to generate oscillations. The oscillation frequency of such a circuit can be controlled by a single [30], a transitron oscillator is used [31] that utilizes a minimal number of components (see Figure 12) capacitor, allowing for simple tuning of such a device although the final circuit deployed to facilitate to generatethe measurement oscillations. of the The resonant oscillation frequency frequency of the sample of such is significantly a circuit can more be complicated. controlled by a single capacitor, allowing for simple tuning of such a device although the final circuit deployed to facilitate the measurement of the resonant frequency of the sample is significantly more complicated.

Figure 12. A simple frequency sweep magnetometer.

Electronics 2017, 6, 89 9 of 21

Figure 11. Non-marginal oscillation utilizing the CA3102 chip. (reproduced with permission from [28]. Copyright AIP, 1977).

Some years later, in 1990, a MOSFET version of a true Robinson oscillator was reported by Wilson and Vallabhan [29]. The use of MOSFETs allows for significant reduction in Q-factor loading of the tank circuit, giving a higher dynamic range for the NMR signal since the shunt impedance of the tank circuit is significantly lower than the input impedance of the MOSFET. They also reduce 1/ noise and, thanks to their good transconductance, can be operated at much lower RF levels.

5.2. Oscillator Circuits Using Frequency Sweep The second type of oscillator, where the magnetic field is constant whilst the sample is driven through resonance by changing the RF frequency, is used extensively for magnetometer applications. This allows for smaller devices (as there are no sweep coils required) and exploration of a greater range of fields than can be achieved by retuning field sweep oscillators. In a 1951 paper by Knoebel [30], a transitron oscillator is used [31] that utilizes a minimal number of components (see Figure 12) to generate oscillations. The oscillation frequency of such a circuit can be controlled by a single capacitor,Electronics 2017 allowing, 6, 89 for simple tuning of such a device although the final circuit deployed to facilitate10 of 21 the measurement of the resonant frequency of the sample is significantly more complicated.

Figure 12. A simple frequency sweep magnetometer. Electronics 2017, 6, 89 Figure 12. A simple frequency sweep magnetometer. 10 of 21

TheThe final final circuit circuit of of the the Knoebel Knoebel and and Hahn Hahn work was modifiedmodified toto utilizeutilize transistorstransistors in in 1966 1966 [ 32[32].]. In In addition addition to to the the replacement replacement of of the the valve valve elemen elements,ts, a aremote remote tuning tuning capacitance capacitance is isadded added as as an electricallyan electrically tuned tuned varicap varicap diode diode (CR1 in (CR1 Figure in Figure13), allowing 13), allowing for an automated for an automated sweep of sweep the frequency of the equivalentfrequency to equivalent the field tosweep the field in the sweep alternative in the alternative class of oscillator. class of oscillator.

FigureFigure 13 13.. AA frequency frequency sweep oscillator utilizingutilizing transistors.transistors.

Varicap diodes are however challenging to work with and do not allow for as wide a tuning Varicap diodes are however challenging to work with and do not allow for as wide a tuning range as desired for maximum convenience. They are however also used in the more recent Robinson range as desired for maximum convenience. They are however also used in the more recent Robinson work [33] for a magnetometer. work [33] for a magnetometer. The same concept can be found for a low field magnetometer presented by Weyand [34], which The same concept can be found for a low field magnetometer presented by Weyand [34], which is is shown in Figure 14, where a pair of back to back varicap diodes are substituted for the original shown in Figure 14, where a pair of back to back varicap diodes are substituted for the original tuning tuning capacitors on the tank circuit allowing for a greater range of tuning and also for accurate tuning at field below 50 mT, which are typically challenging to measure.

Figure 14. Front end of Weyand’s low field magnetometer, utilizing varicap diode tuning. Such designs continue to enjoy commercial success as magnetometers (e.g., Metrolabs precision teslameter PT2025 [35]).

Electronics 2017, 6, 89 10 of 21

The final circuit of the Knoebel and Hahn work was modified to utilize transistors in 1966 [32]. In addition to the replacement of the valve elements, a remote tuning capacitance is added as an electrically tuned varicap diode (CR1 in Figure 13), allowing for an automated sweep of the frequency equivalent to the field sweep in the alternative class of oscillator.

Figure 13. A frequency sweep oscillator utilizing transistors.

Varicap diodes are however challenging to work with and do not allow for as wide a tuning range as desired for maximum convenience. They are however also used in the more recent Robinson workElectronics [33]2017 for, 6a, 89magnetometer. 11 of 21 The same concept can be found for a low field magnetometer presented by Weyand [34], which is shown in Figure 14, where a pair of back to back varicap diodes are substituted for the original tuningcapacitors capacitors on the tankon the circuit tank allowingcircuit allowing for a greater for a rangegreater of range tuning of and tuning also forand accurate also for tuningaccurate at tuningfield below at field 50 mT,below which 50 mT, are which typically are challengingtypically challenging to measure. to measure.

Figure 14. Front end of Weyand’s low field magnetometer, utilizing varicap diode tuning. Figure 14. Front end of Weyand’s low field magnetometer, utilizing varicap diode tuning. Such designs continue to enjoy commercial success as magnetometers (e.g., Metrolabs precision teslameterSuch designsPT2025 continue[35]). to enjoy commercial success as magnetometers (e.g., Metrolabs precision teslameter PT2025 [35]). An alternative circuit design known as a Q-meter have been used increasingly in low temperature experiments to investigate processes such as chemical group rotation since the 1980s [36]. Such circuits use similar detection processes where the absorption or dispersion signals, or both, are recorded at a range of frequencies [37] with double lock in detection to sweep the tuning of the circuit with the applied RF, thus measuring the circuit Quality, Q. By changing the phase of the lock-in amplifier employed in such a configuration, the dispersion and absorption can be simultaneously recorded. In addition to low temperature experiments, Q-meters have also been used more recently for nuclear and particle physics experiments where similar devices are used to measure the polarisation of metallic targets held at low temperatures in magnetic fields [38]. In more recent years, developments have been made to improve the noise levels of such devices particularly for non-proton signals and those which result from polarisation driven by Dynamic Nuclear Polarisation (DNP) [39]. In such experiments, the sample is irradiated with microwaves, which results in electron excitation. The energy of the excited electrons is then transferred to the nuclei of interest by various processes. CW-NMR provides a highly sensitive method of detection of the level of polarisation that is affected by nuclear irradiation thus allowing indirect detection of changes to the sample.

6. Relaxation Measurements with CW-NMR Although rarely performed given the prevalence of pulsed magnetic resonance, it is possible to measure both the spin-lattice relaxation time T1 (the time constant of the loss of energy to the surrounding lattice) and the spin-spin relaxation time T2* (not actually a loss of energy, but the time constant of the loss of phase between neighboring nuclei) of a sample, both of which provide characteristic information. In the coming subsections, we will review strategies for measuring these time constants and their applications.

6.1. Measuring the Spin-Lattice Relaxation Time Constant

The return of the excited nuclei to their equilibrium state occurs with a time constant T1, the measurement of which is notoriously time consuming with pulsed magnetic resonance. Several ingenious methods of measuring this value with continuous wave magnetic resonance have been published in the literature. One of the first experiments measuring T1 was published in 1949 by Drain [40] and is an extension of the original work by Bloch [11]. The principle of detection is that with two crossed coils, one used Electronics 2017, 6, 89 12 of 21 to excite the sample and one to detect the resulting absorption, the time at which the absorption is measured dictates the polarity of the signal. During the course of a sweep cycle, the magnetisation tends towards equilibrium exponentially. Where the sweep rate is on the same order as the T1 time, this change will be happening whilst the system is above and below resonance. When the sweep voltage is balanced about resonance, the peak generated sweeping from low to high will have the same amplitude as the peak sweeping back. If the sweep voltage is offset above or below resonance however, the two peaks will have different . Plotting the amplitude of either of these peaks as a function of the difference between the time spent above and below resonance results in a trace of the T1 relaxation. The author goes on to verify this with measurements of the T1 value for glycerine protons at different temperatures and hence viscosities. An alternative strategy, such as that used in the work of [13] is to drive the sample with a very low RF signal such that it takes several sweeps through resonance to cause saturation of the nuclei of interest. In this experiment, each absorption trace is collected and plotted as a function of the integral of the applied RF. The amplitude of the absorption traces will change exponentially with T1. This method, although relatively accurate, requires an exact measurement of the RF field. In a strategy more akin to pulsed NMR’s inversion recovery experiment, the sample is saturated on resonance and quickly swept off resonance for a time and then swept back through resonance [13]. The amplitude is plotted against the time between sweeps which again yields an exponential with timeElectronics constant 2017, 6, T 891. This is an excellent method for easily saturated samples with very long T1 values,12 of 21 ideally well over 5 s. A similar method, presented in 1983 by Firth [41], uses a commercial Newport magnetometersaturated either based with onsignificant a Robinson RF power oscillator. or lo Beforew modulation the start amplitude. of the experiment, The saturation the sample is then is saturatedsuddenly reduced either with (either significant by reducing RF power the RF or power low modulation or increasing amplitude. the modulation The saturation amplitude). is thenThe suddenlysignal recovers reduced with (either a time by constant reducing ZT the1, where RF power Z = (1 or+ 2PT increasing1) − 1 and the P modulationis the probability amplitude). of inducing The signala nuclear recovers transition with afor time the constant nuclei ZTof 1interest, where Z(w =hich (1 + 2PTshould1) − technically1 and P is the be probability a function of of inducing the RF aintensity nuclear and transition field magnitude, for the nuclei which of interest is not (whichincluded should here technicallyas it was not be in a functionthe original of the work). RF intensity Such a andrecovery field magnitude,was recorded which with is an not oscilloscope included here camera as it wasby way not inof thedemonstration, original work). which Such is ashown recovery in wasFigure recorded 15. with an oscilloscope camera by way of demonstration, which is shown in Figure 15.

Figure 15. Oscilloscope trace of the proton recovery of water. (reproduced with permission from [41]. Figure 15. Oscilloscope trace of the proton recovery of water. (reproduced with permission from [41]. Copyright IOP, 1982). Copyright IOP, 1982).

An elegant measurement of T1 was presented by Donnally in 1963 [42], where different flow An elegant measurement of T was presented by Donnally in 1963 [42], where different flow rates rates of the sample down a pipe are1 used to vary the amount of time that the sample spends in the of the sample down a pipe are used to vary the amount of time that the sample spends in the presence presence of the field. The sample passes through a coil connected to the marginal oscillator described of the field. The sample passes through a coil connected to the marginal oscillator described in their in their earlier paper [23], a schematic for which can be seen in Figure 16. The nuclear spins of the earlier paper [23], a schematic for which can be seen in Figure 16. The nuclear spins of the sample are sample are unaligned while outside of the magnetic field and become polarized as they enter unaligned while outside of the magnetic field and become polarized as they enter (exponentially with (exponentially with time constant T1). For very rapid flow rates, the sample has had little time to time constant T ). For very rapid flow rates, the sample has had little time to become polarized and become polarized1 and hence will have a small signal and as the flow rate becomes smaller the signal increases up to the time at which the sample is fully polarized, after which decreases in flow rates will not increase the signal amplitude. By plotting the signal amplitude against the time from the edge to the center of the magnet, an exponential with time constant T1 is traced. Using this method, the authors measure T1 down to 0.2 s.

Figure 16. The experimental arrangement, described by Donnally, for measuring T1 using a varied flow.

An alternative method proposed in 1968 by Look and Locker [43] utilized a gated sweep waveform. In this method, the sample is left aligned with the magnetic field, which is held off resonance before the start of the measurement. A number of cycles of the sweep coils follow during which each absorption trace is collected.

Electronics 2017, 6, 89 12 of 21

saturated either with significant RF power or low modulation amplitude. The saturation is then suddenly reduced (either by reducing the RF power or increasing the modulation amplitude). The signal recovers with a time constant ZT1, where Z = (1 + 2PT1) − 1 and P is the probability of inducing a nuclear transition for the nuclei of interest (which should technically be a function of the RF intensity and field magnitude, which is not included here as it was not in the original work). Such a recovery was recorded with an oscilloscope camera by way of demonstration, which is shown in Figure 15.

Figure 15. Oscilloscope trace of the proton recovery of water. (reproduced with permission from [41]. Copyright IOP, 1982).

An elegant measurement of T1 was presented by Donnally in 1963 [42], where different flow rates of the sample down a pipe are used to vary the amount of time that the sample spends in the presence of the field. The sample passes through a coil connected to the marginal oscillator described Electronicsin their2017 earlier, 6, 89 paper [23], a schematic for which can be seen in Figure 16. The nuclear spins13 of of 21the sample are unaligned while outside of the magnetic field and become polarized as they enter hence(exponentially will have awith small time signal constant and as T the1). flowFor very rate becomesrapid flow smaller rates, the the signal sample increases has had up little to the time time to atbecome which thepolarized sample and is fully hence polarized, will have after a small which signal decreases and as in the flow flow rates rate will becomes not increase smaller the the signal signal amplitude.increases up By plottingto the time the at signal which amplitude the sample against is fully the timepolarized, from the after edge which to the decreases center of in the flow magnet, rates will not increase the signal amplitude. By plotting the signal amplitude against the time from the an exponential with time constant T1 is traced. Using this method, the authors measure T1 down to 0.2edge s. to the center of the magnet, an exponential with time constant T1 is traced. Using this method, the authors measure T1 down to 0.2 s.

Figure 16. The experimental arrangement, described by Donnally, for measuring T using a varied flow. Figure 16. The experimental arrangement, described by Donnally, for measuring 1T1 using a varied flow.

ElectronicsAnAn alternative alternative2017, 6, 89 method method proposed proposed in 1968 in by 1968 Look by and Look Locker and [43] Locker utilized a[43] gated utilized sweep waveform. a gated13 of 21 Insweep this method, waveform. the sample In isthis left method, aligned with the the sample magnetic is field,left aligned which is held with off the resonance magnetic before field, the startThe of amplitudes the measurement. of each A number trace ofvary cycles exponentially of the sweep coils with follow time during constant which T each1 (see absorption some which is held off resonance before the start of the measurement. A number of trace is collected. The amplitudesexample of each trace traces vary in exponentially Figure 17 with time constant T1 (see some examplecyclesFigure traces of ) until the in Figure saturationsweep 17) coils until is reached. saturationfollow Such during is reached. a method wh Suchich was each a methodrelatively absorption was easy relatively to traceautomate easy is collected. toeven automate in the evenlate 60s, in the although late 60s, automatic although processing automatic processingwas not available. was not available.

Figure 17.17.Example Example traces traces from from the Lookthe Look andLocker and Locker experiment. experiment. Each peak Each is an peak individual is an absorptionindividual signalabsorption collected signal after collected n full after cycles n offull the cycles sweep of the signal sweep showing signal anshowing exponential an exponential reduction reduction in signal amplitude.in signal amplitude. The left The figure left is figure the signal is thefrom signal protons from protons in water, in water, the right the figure right figure is the is signal the signal from Fluorinefrom Fluorine in Calcium in Calcium Fluoride. Fluoride. (reproduced (reproduced with permission with permission from [43 from]. Copyright [43]. Copyright American American Physical Society,Physical 1968). Society, 1968).

6.2. Measuring the Spin-Spin Relaxation Time ConstantConstant InIn a pulsed experiment, experiment, the the direction direction of of some some of of th thee nuclei nuclei of of interest interest are are aligned aligned and and allowed allowed to toprecess. precess. As Asthey they do do so, so, they they generate generate a aminiscule miniscule field field that that perturbs perturbs their their neighbors, leading to fractionallyfractionally different precessionalprecessional frequencies.frequencies. Ov Overer time (from microseconds to a few seconds in most samples), the number of nucleinuclei rotatingrotating throughthrough thethe originaloriginal pointpoint everyevery revolutionrevolution decreasesdecreases exponentially. WhereWhere thisthis cancan bebe measured,measured, thethe timetime constantconstant is knownknown as T2*T2* inin aa continuouscontinuous wave system, energy is suppliedsupplied off resonance,resonance, whichwhich has littlelittle if nono effecteffect onon thethe nucleinuclei ofof interest.interest. At the pointpoint atat which which we we approach approach resonance, resonance, we beginwe begin to affect to theaffect nuclei. the Asnuclei. we then As sweepwe then past sweep resonance, past theresonance, signal maythe signal continue may to continue exist thanks to exist to thisthanks T2* to storage this T2* of st energy.orage of For energy. samples For with samples long with T2*, thislong will T2*, havethis will a more have significant a more significant effect than effect for th thosean for with those short with T2*.short AsT2*. such, As such, assuming assuming that that the sweepthe sweep of field of field or frequency or frequency is sufficiently is sufficiently slow toslow approximate to approximate the steady the steady state absorption, state absorption, T2* can T2* be determinedcan be determined from the from line widththe line of thewidth absorption of the absorption signal. R2 =signal. (1/T2*) R2 is= proportional(1/T2*) is proportional to the half-height to the half-height width of the absorption peak or the interval between the maximum and minimum slope. A particularly nice treatment of the numerical form for both Gaussian and Lorentz absorption line shapes is provided by Andrew [13]. Such measurements have been used for wide ranging applications such as Iron concentration measurements and glycerin viscosity and temperature variation [39]. An alternative method for determining T2* is presented by Bloembergen et al. [19], utilizing a beat signal termed wiggles. This beat signal is caused by the increasing difference between the frequency of the nuclei that are still precessing, which increases as the field sweep continues, and the RF excitation frequency. This leads to a signal (grey in Figure 18) which decreases exponentially with T2* and which becomes increasingly higher in frequency as a function of the sweep rate [44].

Figure18. Beating caused by differences in the frequency of rotation of precessing nuclei and RF excitation.

Electronics 2017, 6, 89 13 of 21

The amplitudes of each trace vary exponentially with time constant T1 (see some example traces in Figure 17 Figure ) until saturation is reached. Such a method was relatively easy to automate even in the late 60s, although automatic processing was not available.

Figure 17. Example traces from the Look and Locker experiment. Each peak is an individual absorption signal collected after n full cycles of the sweep signal showing an exponential reduction in signal amplitude. The left figure is the signal from protons in water, the right figure is the signal from Fluorine in Calcium Fluoride. (reproduced with permission from [43]. Copyright American Physical Society, 1968).

6.2. Measuring the Spin-Spin Relaxation Time Constant In a pulsed experiment, the direction of some of the nuclei of interest are aligned and allowed to precess. As they do so, they generate a miniscule field that perturbs their neighbors, leading to fractionally different precessional frequencies. Over time (from microseconds to a few seconds in most samples), the number of nuclei rotating through the original point every revolution decreases exponentially. Where this can be measured, the time constant is known as T2* in a continuous wave system, energy is supplied off resonance, which has little if no effect on the nuclei of interest. At the point at which we approach resonance, we begin to affect the nuclei. As we then sweep past resonance, the signal may continue to exist thanks to this T2* storage of energy. For samples with long T2*, this will have a more significant effect than for those with short T2*. As such, assuming that

Electronicsthe sweep2017 of, 6field, 89 or frequency is sufficiently slow to approximate the steady state absorption,14 ofT2* 21 can be determined from the line width of the absorption signal. R2 = (1/T2*) is proportional to the half-height width of the absorption peak or the interval between the maximum and minimum slope. widthA particularly of the absorption nice treatment peak or of the the interval numerical between form the for maximum both Gaussian and minimum and Lorentz slope. absorption A particularly line niceshapes treatment is provided of the numericalby Andrew form [13]. for bothSuch Gaussian measurements and Lorentz have absorption been used line for shapes wide is providedranging byapplications Andrew [13such]. Suchas Iron measurements concentration have measurements been used for and wide glycerin ranging viscosity applications and suchtemperature as Iron concentrationvariation [39]. measurements and glycerin viscosity and temperature variation [39]. An alternativealternative methodmethod for for determining determining T2* T2* is is presented presented by by Bloembergen Bloembergen et al. et [ 19al.], [19], utilizing utilizing a beat a signalbeat signal termed termed wiggles. wiggles. This beat This signal beat is signal caused is by caused the increasing by the differenceincreasing betweendifference the between frequency the of thefrequency nuclei thatof the are nuclei still precessing, that are still which precessing, increases wh asich the increases field sweep as the continues, field sweep and continues, the RF excitation and the frequency.RF excitation This frequency. leads to a This signal leads (grey to ina signal Figure (grey 18) which in Figure decreases 18) which exponentially decreases withexponentially T2* and which with becomesT2* and which increasingly becomes higher increasingly in frequency higher as in a functionfrequency of as the a sweepfunction rate of [the44]. sweep rate [44].

FigureFigure18. 18. BeatingBeating caused caused by differences by differences in the frequency in the frequency of rotation of of rotation precessing of nuclei precessing and RF nuclei excitation. and RF excitation.

Such a signal will be seen where the sweep rate does not approximate the steady state, i.e., is short compared with 1/γ∆H0, where ∆H0 is the inhomogeneity in the field. Useful guidance is provided [45], suggesting that the sweep must be at least ten times faster than the shortest T2* value of interest to achieve such a signal. In the literature, this experiment is often referred to as the fast passage experiment. As the inhomogeneity of the field increases, the distribution of precessional frequencies causes an additional beat frequency such as that seen in the Black curve of Figure 18, which are reviewed in the publication of Gabillard [46]. As the inhomogeneity continues to increase, it becomes progressively more difficult to meet the criteria for fast passage and it ultimately becomes impossible to measure T2* using such a method. There are remarkably few reports past the 1960s of CW-NMR being used for T2* measurements. Given the prevalence of monitoring T2* with pulsed NMR for industrial applications, one would expect that a technique that would allow T2* to be measured for a small fraction of the cost of a commercial pulsed system would be commonplace, but this is not the case. Even CW-NMR teaching instruments avoid the measurement of T2* in their guidance literature. The stringent requirements for high field homogeneity (required to satisfy the condition by which the sweep rate is short compared to 1/γ∆H0) are most likely the reason for this, combined with the difficulty of determining the value of T2* which is straightforward with pulsed NMR.

6.3. Amplitude Measurements Although high resolution FT-NMR offers qualitative answers to complex, structure oriented problems in chemistry and physics, amplitude measurements of CW-NMR offer a solution that is both easier to implement and interpret for high throughput, quantitative analysis. As well as offering a simple nucleus-counting tool (where the amplitude of a signal is proportional to the number of contributing, precessing magnetic moments), atoms of a solid have a restricted motion compared to those of a liquid. This restriction is reflected in the resonance profile of the magnetic moments, with a broad resonance associated with solids, and a narrow peak with liquids, with Electronics 2017, 6, 89 15 of 21 integrals proportional to the number of nuclei. This difference in line-shape then allows isolation of the individual components of the signal using suitable filters and adjustment of the NMR instrumentation. The ability to differentiate between states of matter, particularly bound and unbound water, prompted many agricultural, industrial and food based applications in CW-NMR. Early examples of this looked at signal amplitude to evaluate the water content of foodstuffs such as apple and potato [47]. An interesting example [48] also presented an experiment where the proton signal in coal is first determined before the sample is wetted. After the ingress of water, an additional sharper Electronicsresonance 2017 is, 6 seen, 89 effectively overlaid atop the original coal signal (see Figure 19). 15 of 21

FigureFigure 19. 19. DashedDashed line line is absorption is absorption signal signal from fromdry coal dry as coal a result asa of result naturally of naturally present protons. present The protons. solid lineThe follows solid line the ingress follows of the water. ingress Notice of water.the shoulder Notice on the the shouldersolid line as on a theresult solid of the line original as a result protons. of the original protons. The amplitude measurement that is most widely used is for an alternative design of magnetometerThis was followedto that described by investigations previously, of liquid-to-solid where instead ratio, of sweeping initially in the chocolate frequency [49], to using find the a resonance,amplitude a of pre-polarised the wide-line sample peak associated is detected with remo thetely hydrogen from the signal field ofin fat.a traditional This wide-line CW-NMR method at fixedwas alsofrequency compared [55]. The to traditional amplitudeways of the ofabsorption measuring signal fat contentin the remote at the CW-NMR time, such is asthen dilatometry inversely proportional(a measure of to the the change field ofof sizeinterest. of a sampleIn the aswork a function of Woo, of the temperature) setup is improved and was shownto allow to befor more the measurementsreliable [50]. Dynamic of magnetic liquid–solid fields as low ratio as experimentsa few μT [56]. were then used to offer greater information regarding rehydration of foodstuffs [51] thanks to the low experimental time, allowing several 7.non-destructive Advances in Electronics repeats over the course of the dehydration of a sample. FromThese the experiments late 1980s onwards opened the CW-NMR door for became CW-NMR larg methodsely shelved, to evaluate except for other educational dynamic processes,purposes andsuch a asfew the niche oil content applications, of corn kernelsas electronic using adva commercialnces made instruments pulsed magnet such asic the resonance Varian model the more PA7 powerfulanalyser withof the an two integrator techniques. [52] orA thosesmall involvinggroup of researchers fats in the food however industry continued [46] and to the explore effects the of potentialtemperature of this on technique. these processes In this [53 section]. This we method review also a number found application of applications non-invasively and modifications evaluating to thethe original flowing processtechnique, streams which themselves in some [way54] directlyutilize electronics within the productionthat were not line. available during the originalSeveral development commercial period. instruments, such as the Newport Wide-Line Nuclear Magnetic Resonance Analyser or quantity Analyser, were also developed to facilitate industrial measurements for some of 7.1.these Magnetometers applications and for other material samples, although their use was and is very limited. The amplitude measurement that is most widely used is for an alternative design of magnetometer to thatThe describedsensitivity of previously, a magnetometer where is instead dependent of sweepingon the range the of frequencyfields which to it findis measuring a resonance, and, asa such, pre-polarised the smaller sample the sample is detected and RF remotely coil can be, from the thegreater field the in sensitivity a traditional of the CW-NMR instrument. at With fixed afrequency fully miniaturised [55]. The sample amplitude and of coil, the it absorption then becomes signal desirable in the remote to reduce CW-NMR the overall is then size inversely of the electronicsproportional that to drive the fieldthe system. of interest. In 1998, In Boero the work et al. of [57] Woo, developed the setup a CW-NMR is improved device to allow on a chip for theby electrodepositingmeasurements of a magnetic copper spiral fields coil as lowonto as glass a few nextµT[ to56 a]. CMOS integrated bridge circuit (tuned with an MV209 Epicap Diode, On Semiconductor, Pheonix, USA), which undertakes signal amplification and detection, with an approximate overall size of 6 mm × 18 mm. The tuning of the device and frequency sweeping is computer controlled and the signal is digitized with a PC ADC (Analogue to Digital Converter). One of the areas critical to CW-NMR that has seen the greatest development in recent decades is the generation of radio frequency. In the work of Wu et al. [58] for example, a digital RF generation system is used to provide energy to the sample and is also inductively coupled to a marginal oscillator (as described previously) which is used for detection. A Direct Digital Synthesiser (DDS) and Phased Locked Loop (PLL) are controlled by an 8051 microcontroller and generate a frequency sweep. The previous work still utilises oscillator (and therefore analogue) signal detection. In the work of Begus and Fefer [59], attempts are made to replace as many analogue elements as possible with digital versions to improve stability and sensitivity. The system uses a similar front end to that in the original Rollin [12] paper, but with a temperature controlled DDS to supply the RF through a resistor

Electronics 2017, 6, 89 16 of 21

7. Advances in Electronics From the late 1980s onwards CW-NMR became largely shelved, except for educational purposes and a few niche applications, as electronic advances made pulsed magnetic resonance the more powerful of the two techniques. A small group of researchers however continued to explore the potential of this technique. In this section we review a number of applications and modifications to the original technique, which in some way utilize electronics that were not available during the original development period.

7.1. Magnetometers The sensitivity of a magnetometer is dependent on the range of fields which it is measuring and, as such, the smaller the sample and RF coil can be, the greater the sensitivity of the instrument. With a fully miniaturised sample and coil, it then becomes desirable to reduce the overall size of the electronics that drive the system. In 1998, Boero et al. [57] developed a CW-NMR device on a chip by electrodepositing a copper spiral coil onto glass next to a CMOS integrated bridge circuit (tuned with an MV209 Epicap Diode, On Semiconductor, Pheonix, USA), which undertakes signal amplification and detection, with an approximate overall size of 6 mm × 18 mm. The tuning of the device and frequency sweeping is computer controlled and the signal is digitized with a PC ADC (Analogue to Digital Converter). One of the areas critical to CW-NMR that has seen the greatest development in recent decades is the generation of radio frequency. In the work of Wu et al. [58] for example, a digital RF generation system is used to provide energy to the sample and is also inductively coupled to a marginal oscillator (as described previously) which is used for detection. A Direct Digital Synthesiser (DDS) and Phased Locked Loop (PLL) are controlled by an 8051 microcontroller and generate a frequency sweep. The previous work still utilises oscillator (and therefore analogue) signal detection. In the work of Begus and Fefer [59], attempts are made to replace as many analogue elements as possible with digital versions to improve stability and sensitivity. The system uses a similar front end to that in the original Rollin [12] paper, but with a temperature controlled DDS to supply the RF through a resistor to the tank circuit with a voltage tuned capacitor. This signal is then demodulated using the DDS as a reference before utilizing software lock-in detection on a Digital Signal Processor IC. An alternative approach is seen in the work of Geršak et al. [60], which utilizes several benchtop instruments controlled by a PC running LabVIEW (National Instruments, Austin, TX, USA) to generate the necessary signals and collect the resulting spectra using a cross coil system as described previously.

7.2. Imaging Another area that has benefitted greatly from advances in electronics is imaging. Most work in this area is based around the use of hybrid junctions, which are commercially available in various frequencies. The hybrid junction is a long-standing four-arm radio frequency and microwave component, designed such that a signal incident in any one arm is divided between two others, and not present on the fourth. This leads to interesting behavior if two coherent signals are incident on an arm each, as their sum will be present on the third arm and their difference on the fourth. Furthermore, if one of the arms is terminated with an appropriate impedance, one has incident RF and the third is connected to a circuit which absorbs the RF energy, the fourth arm will have an RF voltage proportional to the amount of energy that has been used. In this way, such a system can be seen as a type of bridge circuit if a tank circuit and terminator are connected to two branches, with an RF on a third. If there is an impedance mismatch between the terminator and a tank circuit (with the inductor containing the sample), the fourth branch outputs an RF voltage inversely proportional to the absorption. Such a circuit can be seen at the heart of a design by Lurie for imaging solids [61], followed by rectification with a diode detector. In the Lurie paper [61], and more recently in an extension of this work to image in three dimensions by Fagan [62], a small audio (1 kHz) is Electronics 2017, 6, 89 16 of 21

to the tank circuit with a voltage tuned capacitor. This signal is then demodulated using the DDS as a reference before utilizing software lock-in detection on a Digital Signal Processor IC. An alternative approach is seen in the work of Geršak et al. [60], which utilizes several benchtop instruments controlled by a PC running LabVIEW (National Instruments, Austin, TX, USA) to generate the necessary signals and collect the resulting spectra using a cross coil system as described previously.

7.2. Imaging Another area that has benefitted greatly from advances in electronics is imaging. Most work in this area is based around the use of hybrid junctions, which are commercially available in various frequencies. The hybrid junction is a long-standing four-arm radio frequency and microwave component, designed such that a signal incident in any one arm is divided between two others, and not present on the fourth. This leads to interesting behavior if two coherent signals are incident on an arm each, as their sum will be present on the third arm and their difference on the fourth. Furthermore, if one of the arms is terminated with an appropriate impedance, one has incident RF and the third is connected to a circuit which absorbs the RF energy, the fourth arm will have an RF voltage proportional to the amount of energy that has been used. In this way, such a system can be seen as a type of bridge circuit if a tank circuit and terminator are connected to two branches, with an RF on a third. If there is an impedance mismatch between the terminator and a tank circuit (with the inductor containing the sample), the fourth branch outputs an RF voltage inversely proportional to the absorption. Such a circuit can be seen at the heart of a design by Lurie for imaging solids [61], followed by rectification with a diode detector. In the Lurie paper [61], and more recently in an Electronics 2017, 6, 89 17 of 21 extension of this work to image in three dimensions by Fagan [62], a small audio frequency modulation (1 kHz) is superimposed in the magnetic field sweep voltage. The output of the diode superimposeddetector is then in fed the to magnetic the input field of a sweep lock-in voltage. amplif Theier with output the ofsame the diode1 kHz detectorsignal used is then as a fed reference, to the inputthus ofalmost a lock-in eliminating amplifier the with noise the and same amplifying 1 kHz signal only used the as NMR a reference, signal, thusa schematic almost eliminatingfor which is thedisplayed noise and in Figure amplifying 20. This only is essential the NMR in signal,the case a of schematic imaging as for the which already is displayedminimal signal in Figure is further 20. Thisminimized is essential given in the localization case of imaging of magnetic as the already moments minimal of interest signal by isthe further 3D gradient minimized coils, given which the are localizationalso included. of magnetic moments of interest by the 3D gradient coils, which are also included.

FigureFigure 20. 20.Block Block diagram diagram of of a a setup setup for for 3 3 dimensional dimensional continuous continuous wave wave NMR NMR imaging. imaging. (reproduced (reproduced withwith permission permission from from [62 [62]]. Copyright. Copyright Elsevier, Elsevier, 2005). 2005).

7.3.7.3. Updated Updated Measurements Measurements of of Relaxation Relaxation Parameters Parameters WeWe have have recentlyrecently presented an an updated updated measurement measurement method method [63] [63 based] based on onthe thework work of Look of Lookand andLocker Locker [43] [43utilizing] utilizing direct direct signal signal capture capture and and sweep sweep signal signal generation withwith aa NationalNational InstrumentsInstruments Data Data Acquisition Acquisition card card and and PC PC to to automatically automatically acquire acquire T 1T1curves. curves. A A method method was was also also proposed to eliminate the effect of the oscillator parameters on the resulting measurements by using end-point calibration.

8. Future Developments One of the most ubiquitous building blocks for modern electronics is the microcontroller, which has become better and better equipped with peripherals as each year passes. The Teensy microcontroller [64] is an excellent example of this which, for less than USD25, has an ADC and DAC (Digital to Analogue Converter) which runs at 18 MHz. These are also easily extended with a plethora of extra modules that bring additional functionality. In Figure 21 we show typical data from a teaching CW-NMR system (LD Didactic GmbH, Hürth, Germany) with a sample of 20 cS PDMS oil and digitization of the signal resulting from the relaxation measurement described in [63]. The sweep coil rate is set at 10 Hz and the audio capture rate is set to 44.1 kHz, with 16 bit data saved to a raw file based on the example code provided at [65]. The Teensy and audio shield together cost approximately USD35, providing an exceptionally cost-effective data capture package, although alternatives are available such as the Raspberry PI [66] with a sound card. The ability to make an entire NMR based detection system for less than USD 200 will allow exploration of a wide array of new applications for which NMR was previously too expensive. Electronics 2017, 6, 89 17 of 21

proposed to eliminate the effect of the oscillator parameters on the resulting measurements by using end-point calibration.

8. Future Developments One of the most ubiquitous building blocks for modern electronics is the microcontroller, which has become better and better equipped with peripherals as each year passes. The Teensy microcontroller [64] is an excellent example of this which, for less than USD25, has an ADC and DAC (Digital to Analogue Converter) which runs at 18 MHz. These are also easily extended with a plethora of extra modules that bring additional functionality. In Figure 21 we show typical data from a teaching CW-NMR system (LD Didactic GmbH, Hürth, Germany) with a sample of 20 cS PDMS oil and digitization of the signal resulting from the relaxation measurement described in [63]. The sweep coil rate is set at 10 Hz and the audio capture rate is set to 44.1 kHz, with 16 bit data saved to a raw file based on the example code provided at [65]. The Teensy and audio shield together cost approximately USD35, providing an exceptionally cost-effective data capture package, although alternatives are available such as the Raspberry PI [66] with a sound card. The ability to make an entire NMR based detection system for less than USD 200 will allow exploration of a wide array of Electronics 2017, 6, 89 18 of 21 new applications for which NMR was previously too expensive.

FigureFigure 21.21. ExampleExample datadata toto showshow howhow relaxationrelaxation measurementsmeasurements cancan bebe obtainedobtained usingusing lowlow costcost microcontrollermicrocontroller capture. capture.

WhilstWhilst using using electromagnets electromagnets gives gives flexibility flexibility in in the the choice choice of of magnetic magnetic field field and and hence hence operating operating frequency,frequency, they they also also are are bulky, bulky, expensive expensive and and consume consume significant significan power.t power. Permanent Permanent magnets magnets are less are flexibleless flexible and suffer and fromsuffer temperature from temperature drift but drift require but no require external no power external source power and hencesource consume and hence no consume no power. Modern magnet technology, particularly that using Neodymium Iron Boron power. Modern magnet technology, particularly that using Neodymium Iron Boron (NdFeB) magnets, (NdFeB) magnets, do however provide small size, low-cost magnets in the field range that equates to do however provide small size, low-cost magnets in the field range that equates to a NMR frequency a NMR frequency up to 20 MHz. There have been many reports over the years of how to achieve field up to 20 MHz. There have been many reports over the years of how to achieve field uniformity uniformity from permanent magnets, including the use of pole pieces [67], or with current from permanent magnets, including the use of pole pieces [67], or with current developments in 3D developments in 3D printing offering exciting potential for a simple route to custom design such printing offering exciting potential for a simple route to custom design such magnets directly [68]. magnets directly [68]. Similarly, magnet designs for pulsed NMR have become sufficiently Similarly, magnet designs for pulsed NMR have become sufficiently homogeneous for achieving homogeneous for achieving spectroscopy [69,70], which should also be sufficient for CW-NMR spectroscopy [69,70], which should also be sufficient for CW-NMR relaxation time measurements. relaxation time measurements. In Figure 22, we show the electromagnets in a teaching CW-NMR In Figure 22, we show the electromagnets in a teaching CW-NMR system (LD Didactic GmbH, Hürth, system (LD Didactic GmbH, Hürth, Germany) replaced with a pair of low-cost NdFeB magnets with Germany) replaced with a pair of low-cost NdFeB magnets with the NMR signal from water on the NMR signal from water on the oscilloscope. theElectronics oscilloscope. 2017, 6, 89 18 of 21

Figure 22. Electromagnets can be substituted for low-cost, modern NdFeB magnets.

9. Conclusions 9. Conclusions In this article we have reviewed the electronics required to make measurements of various In this article we have reviewed the electronics required to make measurements of various samples using continuous wave NMR. CW-NMR will never directly compete with pulsed NMR samples using continuous wave NMR. CW-NMR will never directly compete with pulsed NMR systems in providing a universal tool capable of measurements over a wide range of T1, T2* and T2eff systems in providing a universal tool capable of measurements over a wide range of T ,T * and T eff or in measuring diffusion and over a range of magnetic fields. It does however provide1 2an exciting2 or in measuring diffusion and over a range of magnetic fields. It does however provide an exciting opportunity for easily automated, low cost measurement applications. Although Pulsed NMR has opportunity for easily automated, low cost measurement applications. Although Pulsed NMR has been shown to be an effective analysis tool for the food and drinks industries (see for example recent been shown to be an effective analysis tool for the food and drinks industries (see for example recent reviews [71,72]), the limitations of cost, complexity and power consumption of pulsed techniques reviews [71,72]), the limitations of cost, complexity and power consumption of pulsed techniques have to a large extent consigned these to the literature. We have shown however that where there is have to a large extent consigned these to the literature. We have shown however that where there a targeted application for which the measurement range is clearly defined, CW-NMR may now be is a targeted application for which the measurement range is clearly defined, CW-NMR may now capable of providing a cost effective industrial solution. Challenges still lie in the continued development of homogeneous magnets, perhaps with pole pieces displaying sufficient homogeneity or T2* measurements, however the range of electronics readily available, including low-cost DDS, microcontrollers, advanced amplification blocks, voltage controlled variable capacitors and hybrid junctions, does require a fresh look at Continuous Wave Nuclear Magnetic Resonance in a range of sectors.

Acknowledgments:The authors wish to thank Elizabeth Dye for proof reading of the manuscript.

Author Contributions: All authors contributed equally to the research for and preparation of the manuscript.

Conflicts of Interest: The authors declare no conflict of interest.

References

1. Fox, M.; Rabi, I.I. On the Nuclear Moments of Lithium, Potassium, and Sodium. Phys. Rev. 1935, 48, 746–751. 2. Breit, G.; Rabi, I.I. Measurement of Nuclear Spin. Phys. Rev. 1931, 38, 2082–2083. 3. Purcell, E.M.; Torrey, H.C.; Pound, R.V. Resonance Absorption by Nuclear Magnetic Moments in a Solid. Phys. Rev. 1946, 69, 37–38. 4. Bloch, F.; Hansen, W.W.; Packard, M. Nuclear Induction. Phys. Rev. 1946, 70, 460–474. 5. Mansfield, P. Multi-planar image formation using NMR spin echoes. J. Phys. C Solid State Phys. 1977, 10, 55–58. 6. Arnold, J.T.; Packard, M.E. Variations in Absolute Chemical Shift of Nuclear Induction Signals of Hydroxyl Groups of Methyl and Ethyl Alcohol. J. Chem. Phys. 1951, 19, 1608–1609. 7. Carr, H.; Purcell, E. Effect of Diffusion on Free Precession in Nuclear Magnetic Resonance Experiments. Phys. Rev. 1954, 94, 630–638. 8. Lauterbur, P.C. C13 Nuclear Magnetic Resonance Spectra. J. Chem. Phys. 1957, 26, 217–218. 9. Damadian, R. Apparatus and method for detecting cancer in tissue. U.S. Patent 3789832, 5 February 1974. 10. Larmor, J. LXIII. On the theory of the magnetic influence on spectra; and on the radiation from moving ions. Philos. Mag. 1897, 44, 503–512. 11. Bloch, F.; W. Hansen, W.; Packard, M. The Nuclear Induction Experiment. Am. Phys. Soc. 1946, 70, 474–485.

Electronics 2017, 6, 89 19 of 21 be capable of providing a cost effective industrial solution. Challenges still lie in the continued development of homogeneous magnets, perhaps with pole pieces displaying sufficient homogeneity or T2* measurements, however the range of electronics readily available, including low-cost DDS, microcontrollers, advanced amplification blocks, voltage controlled variable capacitors and hybrid junctions, does require a fresh look at Continuous Wave Nuclear Magnetic Resonance in a range of sectors.

Acknowledgments: The authors wish to thank Elizabeth Dye for proof reading of the manuscript. Author Contributions: All authors contributed equally to the research for and preparation of the manuscript. Conflicts of Interest: The authors declare no conflict of interest.

References

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