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Signal-to-Noise and Magnetic Susceptibility Trade-offs in Solenoidal Microcoils for NMR
JOURNAL OF MAGNETIC RESONANCE, ARTICLE NO.
Series B 113, 83–87 (1996)
0159
COMMUNICATIONS Signal-to-Noise and Magnetic Susceptibility Trade-offs in Solenoidal Microcoils for NMR A. G. WEBB
AND
S. C. GRANT
Magnetic Resonance Engineering Laboratory, Department of Electrical and Computer Engineering, University of Illinois at Urbana–Champaign, 1406 West Green Street, Urbana, Illinois 61801 Received July 1, 1996; revised July 15, 1996
the coil. However, the filling factor of this coil was less than 5%, meaning that high concentrations were necessary to achieve sufficient signal-to-noise (S/N). In this Communication, we show that the filling factor of solenoidal microcoils can be increased by up to a factor of seven, corresponding to a reduction in data acquisition time of 50-fold, with minimal degradation in the spectral resolution. We anticipate that these new coils will be particularly important in studying both biological molecules that can only be used in very low concentrations and molecules with low solubility. We also show that the filling factor can be increased further, to greater than 50%, but the linewidths achieved increased to more than 3 Hz. Solenoidal microcoils were constructed by wrapping wire around fused silica capillaries. The wire used was 50 mm diameter, 99.99% copper (California Fine Wire, Grover Beach, California), and was coated with 6 mm thick polyurethane. The fused silica capillaries (Polymicro, Phoenix, Arizona) were available with various outer diameters and wall thicknesses, and were used without removal of the polyimide coating. The capillaries were first wiped to remove contaminants, rinsed under a high-pressure water jet, washed with deionized water, sprayed with compressed air to remove dust, and allowed to dry. The capillary was then centered in a pin vise and the pin-vise holder was tilted upward at an angle of approximately 207. A 5 cm length of wire, weighted at both ends, was draped over the capillary for two turns. The wire was glued to the capillary using nonpermanent cyanoacrylate adhesive and allowed to dry. One weight (3.0 g) was then removed, and the pin vise was rotated to start wrapping the coil. Details of the actual wrapping process have been published elsewhere (14, 15). For an n-turn coil, 12 / n turns were wrapped, and the final turn was glued with permanent adhesive. The nth from final turn was glued with the nonpermanent adhesive and the entire assembly was allowed to dry. In the final step, the remaining weight was removed, the extra turns were unwound up to the nth from
In this paper we show how the filling factor, and therefore the signal-to-noise ratio, of very small solenoidal microcoils can be increased by almost an order of magnitude compared to previously published results, with minimal degradation of spectral resolution. We also empirically determine at what dimensions the magnetic susceptibility of the coil materials produces substantial line broadening in high-resolution spectra. Nuclear magnetic resonance spectroscopy is one of the most powerful methods available for determining molecular structure. Relative to many other analytical techniques, however, it is inherently insensitive. For example, Fourier-transform infrared spectroscopy commonly has limits of detection (LODs) as low as 10 012 to 10 015 mol (1) and mass spectrometry has achieved LODs in the 10 018 mol range (2, 3), but LODs for NMR are typically quoted as 5 1 10 09 mol (4). Many authors have shown that the mass sensitivity can be increased by using NMR ‘‘microcoils,’’ loosely defined as coils having a diameter of 2 mm or less (5–10). There remain, however, fundamental questions concerning the minimum number of spins that can be detected inductively, and still result in high-resolution NMR spectra. Rugar et al. (11) have shown that the mechanical detection schemes proposed by Sidles (12) can significantly reduce the LODs for both electron paramagnetic resonance and NMR. However, due to the inhomogeneous nature of the magnetic field, high-resolution spectroscopy is not yet possible with this technique. Wu et al. (13) used a number of solenoidal microcoils with diameters in the range 355 to 695 mm diameter for both static and dynamic NMR measurements, but only achieved linewidths on the order of 7–10 Hz. The most successful results so far have been obtained by Olson et al. (14), who showed that a solenoidal microcoil (355 mm diameter) increases the mass sensitivity by more than two orders of magnitude when compared with a standard 5 mm probe. High spectral resolution was achieved via a perfluorinated ‘‘susceptibility matching’’ fluid surrounding 83
AID
JMRB 7455
/
6o11$$$281
09-16-96 12:58:02
1064-1866/96 $18.00 Copyright q 1996 by Academic Press, Inc. All rights of reproduction in any form reserved.
magba
AP: Mag Res, Series B
84
COMMUNICATIONS
FIG. 1. Printed-circuit-board layout for positioning the microcoils at the center of the magnet. The fixed matching capacitor (Cm1 ) typically has a value between 1.5 and 2.5 pF. The variable tuning (Ct ) and matching capacitors (Cm2 ) have a range of 1–30 pF.
final turn, and this end was then reglued with permanent adhesive. Using the printed-circuit-board layout shown in Fig. 1, the capillary was centered between the two shoulders. The capillary was glued to the shoulders using permanent adhesive. The wire ends of the coil were soldered to the core and outer casing of the low-magnetic rigid coaxial cable (UT85SS, Rosenberger Micro-coax, Collegeville, Pennsylvania). The connections then were verified using a digital multimeter. A low-density polyethylene bottle was cut and epoxied to the circuit board to allow the coil to be submerged completely in the fluorinert. To tune and match the coil, nonmagnetic fixed (100B2R2PN, American Technical Ceramics, Huntington Station, New York) and variable (Johansen 5641, Boonton, New Jersey) capacitors were used. A fixed matching capacitor (in the range 1.5 to 2.5 pF) was soldered between the rigid coaxial core and the input terminal. Previous work (14) showed that LODs as low as 20 pmol can be achieved by using such solenoidal microcoils. However, the high spectral resolution was accompanied by a very small coil filling factor (approximately 4.4%) for a 355 mm outer diameter (o.d.) and 75 mm inner diameter (i.d.). In order to increase the filling factor, the thickness of the capillary wall must be reduced, meaning that the sample comes closer to the copper windings and the effects of magnetic susceptibility mismatches become more pronounced. To quantify this trade-off between sensitivity and resolution, we constructed a series of coils based on a 355 mm o.d. capillary, but varied the i.d. to alter the filling factor. Seventeen turns were used for all coils, with minimal spacing between the
AID
JMRB 7455
/
6o11$$$282
09-16-96 12:58:02
turns, resulting in a length of approximately 1.1 mm. Eighteen coils in all were tested. Electrical characterization of the coils was performed using a 1–500 MHz network analyzer (Hewlett–Packard, HP 8751). Having calibrated the system to remove the effects of the connecting cable, the coil was tuned to 250 MHz ( f0 ), and the cable soldered directly to the terminals of the coil, bypassing the matching capacitors. The value of the frequencies ( f1 and f2 ) at which the real and reactive components were equal was determined using a Smith Chart. The Q values, Q Å f0 /( f2 0 f1 ) (16), for coils 355 mm in diameter were measured to be between 30 and 35 for every coil tested. It should also be noted that the tuning range of the microcoils was very large. For coils of 355 mm o.d., with one fixed 2 pF capacitor, a 1–30 pF variable matching capacitor, and a 1–30 pF variable tuning capacitor, the range over which the coil can be exactly matched to 50 V was 180–310 MHz. For coils at these dimensions, resistive losses should be coil- rather than sample-dominated, meaning that the coil Q, and therefore S/N, should not be reduced by the introduction of a lossy sample. To demonstrate this, the S11 parameter was measured for a coil of 350/250 mm o.d./i.d. Initially the coil was filled with deionized water, and then successively with 100 and 200 mM sodium chloride solutions. Figure 2 shows the respective plots of S11 versus frequency for each sample. It can be seen that f0 changed by less than 80 kHz for even a highly conducting sample, and the decrease in the loaded versus unloaded Q of the coil was minimal. All NMR experiments were carried out at 250 MHz, using a Tecmag (Houston, Texas) Libra console and 89 mm bore Oxford Instruments magnet (Model 2280). A sample of deionized water was injected into the coil through a short length of Teflon tubing (10). After pulse calibration, the sample was autoshimmed for approximately one hour. The value of the receiver gain was adjusted so that the signal from the solenoid coil with the largest filling factor did not saturate either the mixer stage or the analog-to-digital converter. A Miteq AU-1054 broadband low-noise (1.09 dB noise figure, 32 { 0.3 dB gain) preamplifier (Hauppauge, New York) was placed in front of the mixing stage. A 50 W broadband amplifier (American Microwave Technology, Model M3137, 200–500 MHz) drove the coil, producing an 800 ns 907 pulse at full power for the 355 mm coils. For all spectroscopy experiments, 20 dB transmitter attenuation was introduced, resulting in a 907 pulse of approximately 10 ms. Two experiments were performed to check that radiation damping was not a contributing factor to the measurements: first, varying the tip angle from 57 to 907 resulted in no shift in the resonant frequency of the water peak; second, the linewidth of the peak did not decrease upon coil detuning within the magnet. S/N data were obtained using a spectral width of 10 kHz, 8192 complex data points, a 907 tip angle, and four transients, with CYCLOPS phase cycling (17). The large value
magba
AP: Mag Res, Series B
85
COMMUNICATIONS
FIG. 2. S11 and resonant frequency ( f0 ) for different loading of a 350/250 mm microcoil. (a) Deionized water, S11 Å 041.8 dB, f0 Å 249.95 MHz; (b) 100 mM saline, S11 Å 036.2 dB, f0 Å 249.90 MHz; and (c) 200 m M saline, S11 Å 034.9 dB, f0 Å 249.88 MHz.
of the spectral width was used to avoid baseline artifacts. Data were baseline corrected and Fourier transformed with no apodization. The ratio of the integrated signal intensity of the water peak to the root-mean-square (rms) noise was then calculated. Linewidth measurements were made using a frequency-domain Lorentzian line-fitting algorithm. The spectral width was set at 1000 Hz, with 16,384 complex data points acquired. Four transients were collected, again with CYCLOPS phase cycling. No apodization of the timedomain signal was used. The value of the linewidth reported in Table 1 was the full width at half-maximum (FWHM) of the fitted Lorentzian curve. Three coils were constructed for each inner diameter, and the standard deviation of the linewidth is reported. The data in Table 1 show that for a microcoil with outer diameter 355 mm, the filling factor can be significantly increased from the 4.4% reported previously to 28% with little loss in spectral resolution. A further increase to over 50% significantly increases the linewidth. It should be noted that
AID
JMRB 7455
/
6o11$$$282
09-16-96 12:58:02
the measurements were made on an older magnet than that in Ref. (14), which probably explains the slightly lower resolution obtained using an identical 4.4% filling factor coil. The S/N increases approximately linearly with the filling factor, as would be expected, since end effects are relatively minor. Figure 3 shows spectra obtained from 50 mM
TABLE 1
o.d./i.d. (mm)
Wall thickness (mm)
Filling factor (%)
Relative SNR
355/50 355/75 347/103 354/148 355/180 350/250
152.5 140 122 103 88 50
2.0 4.4 8.8 17.5 28.0 51.0
1.0 2.1 4.1 8.4 13.1 22.3
magba
AP: Mag Res, Series B
LWavg (Hz)
LWmin (Hz)
{ { { { { {
1.1 0.8 1.1 1.0 1.1 3.0
1.2 1.0 1.3 1.1 1.3 3.2
0.3 0.3 0.2 0.3 0.3 0.4
86
COMMUNICATIONS
FIG. 3. Spectra from 50 mM sucrose in D2O. Spectral width {1000 Hz, 8192 complex data points, recycle delay 6 s, 256 scans. The spectra are baseline corrected, and 1 Hz line broadening is applied. (a) 355/75 mm (i.d./o.d.) microcoil, (b) 355/180 mm (i.d./o.d.) microcoil, and (c) 355/250 mm (i.d./o.d.) microcoil.
sucrose in D2O for three coils of different inner diameter. Both the expected increase in S/N and the increased broadening due to the susceptibility mismatch are clearly seen. In conclusion, we have shown that the S/N obtained using previously reported solenoidal microcoils can be increased significantly with little loss in spectral resolution, and therefore the concentration LODs can be reduced by almost an order of magnitude. Coils exhibiting the larger linewidths could find use in on-line coupled NMR detection methods such as liquid chromatography or capillary electrophoresis, where the linewidth is often flow-limited, or in applications where linewidths are naturally large. A number of approaches could be used to improve the lineshape for coils with even larger filling factors. The susceptibility mismatch could be reduced by doping the fused silica capillary such that its susceptibility matches that of the sample. ‘‘Zerosusceptibility’’ wire could also be used, where the diamagnetic susceptibility of copper is canceled out by a paramagnetic material such as rhodium (18) or aluminum (19). This approach was relatively easy at a large scale, but obtaining precise and reproducible doping at small wire diameters remains to be demonstrated.
AID
JMRB 7455
/
6o11$$$282
09-16-96 12:58:02
ACKNOWLEDGMENTS This work was supported by a grant from the National Institutes of Health (PHS 1 RO1 GM53030-01). We acknowledge the assistance and technical support of Drs. Richard Magin (Magnetic Resonance Engineering Laboratory), Timothy Peck (Magnetic Resonance Microsensors Corp.), and Jonathan Sweedler and Dean Olson (School of Chemical Sciences).
REFERENCES 1. C. L. Putzig, Anal. Chem. 66, 26R (1994). 2. O. Vorm, P. Roepstorff, and M. Mann, Anal. Chem. 66, 3281 (1994). 3. A. L. Burlingame, R. K. Boyd, and S. J. Gaskell, Anal. Chem. 66, 634R (1994). 4. A. E. Derome, ‘‘Modern NMR Techniques for Chemistry Research,’’ p. 129, Pergamon Press, New York, 1987. 5. T. M. Barbara, J. Magn. Reson. A 109, 265 (1994). 6. J. S. Schoeniger and S. J. Blackband, J. Magn. Reson. B 104, 127 (1994). 7. Z. H. Cho, C. B. Ahn, S. C. Juh et al., Med. Phys. 15(6), 815 (1988). 8. E. W. McFarland and A. Mortara, Magn. Reson. Imaging 10, 279 (1992). 9. R. W. Wiseman, T. S. Moerland, and J. J. Kushmerik, NMR Biomed. 6, 153 (1993).
magba
AP: Mag Res, Series B
87
COMMUNICATIONS 10. E. Odeblad, ‘‘Micro-NMR in High Permanent Magnetic Fields,’’ Nordisk Forening for Obsterik och Gynekologi, Lund, Sweden, 1966. 11. D. Rugar, O. Zuger, S. Hoen, C. S. Yannoni, H-M. Vieth, and R. D. Kendrick, Science 264, 1560 (1994).
15. T. L. Peck, R. L. Magin, and P. C. Lauterbur, J. Magn. Reson. B 108, 114 (1995). 16. Application Note 154, Hewlett–Packard Co., Palo Alto, California, 1972.
12. J. A. Sidles, Appl. Phys. Lett. 58, 2854 (1991).
17. D. I. Hoult and R. E. Richards, Proc. R. Soc. London Ser. A 344, 311 (1975).
13. N. Wu, T. L. Peck, A. G. Webb, R. L. Magin, and J. V. Sweedler, Anal. Chem. 66, 3849 (1994).
18. F. O. Zelaya, S. Crozier, S. Dodd, R. McKenna, and D. M. Doddrell, J. Magn. Reson. A 115, 131 (1995).
14. D. L. Olson, T. L. Peck, A. G. Webb, R. L. Magin, and J. V. Sweedler, Science 270, 1967 (1995).
19. L. F. Fuks, F. S. Huang, C. M. Carter, W. A. Edelstein, and P. B. Roemer, J. Magn. Reson. 100, 229 (1992).
AID
JMRB 7455
/
6o11$$$282
09-16-96 12:58:02
magba
AP: Mag Res, Series B
Series B 113, 83–87 (1996)
0159
COMMUNICATIONS Signal-to-Noise and Magnetic Susceptibility Trade-offs in Solenoidal Microcoils for NMR A. G. WEBB
AND
S. C. GRANT
Magnetic Resonance Engineering Laboratory, Department of Electrical and Computer Engineering, University of Illinois at Urbana–Champaign, 1406 West Green Street, Urbana, Illinois 61801 Received July 1, 1996; revised July 15, 1996
the coil. However, the filling factor of this coil was less than 5%, meaning that high concentrations were necessary to achieve sufficient signal-to-noise (S/N). In this Communication, we show that the filling factor of solenoidal microcoils can be increased by up to a factor of seven, corresponding to a reduction in data acquisition time of 50-fold, with minimal degradation in the spectral resolution. We anticipate that these new coils will be particularly important in studying both biological molecules that can only be used in very low concentrations and molecules with low solubility. We also show that the filling factor can be increased further, to greater than 50%, but the linewidths achieved increased to more than 3 Hz. Solenoidal microcoils were constructed by wrapping wire around fused silica capillaries. The wire used was 50 mm diameter, 99.99% copper (California Fine Wire, Grover Beach, California), and was coated with 6 mm thick polyurethane. The fused silica capillaries (Polymicro, Phoenix, Arizona) were available with various outer diameters and wall thicknesses, and were used without removal of the polyimide coating. The capillaries were first wiped to remove contaminants, rinsed under a high-pressure water jet, washed with deionized water, sprayed with compressed air to remove dust, and allowed to dry. The capillary was then centered in a pin vise and the pin-vise holder was tilted upward at an angle of approximately 207. A 5 cm length of wire, weighted at both ends, was draped over the capillary for two turns. The wire was glued to the capillary using nonpermanent cyanoacrylate adhesive and allowed to dry. One weight (3.0 g) was then removed, and the pin vise was rotated to start wrapping the coil. Details of the actual wrapping process have been published elsewhere (14, 15). For an n-turn coil, 12 / n turns were wrapped, and the final turn was glued with permanent adhesive. The nth from final turn was glued with the nonpermanent adhesive and the entire assembly was allowed to dry. In the final step, the remaining weight was removed, the extra turns were unwound up to the nth from
In this paper we show how the filling factor, and therefore the signal-to-noise ratio, of very small solenoidal microcoils can be increased by almost an order of magnitude compared to previously published results, with minimal degradation of spectral resolution. We also empirically determine at what dimensions the magnetic susceptibility of the coil materials produces substantial line broadening in high-resolution spectra. Nuclear magnetic resonance spectroscopy is one of the most powerful methods available for determining molecular structure. Relative to many other analytical techniques, however, it is inherently insensitive. For example, Fourier-transform infrared spectroscopy commonly has limits of detection (LODs) as low as 10 012 to 10 015 mol (1) and mass spectrometry has achieved LODs in the 10 018 mol range (2, 3), but LODs for NMR are typically quoted as 5 1 10 09 mol (4). Many authors have shown that the mass sensitivity can be increased by using NMR ‘‘microcoils,’’ loosely defined as coils having a diameter of 2 mm or less (5–10). There remain, however, fundamental questions concerning the minimum number of spins that can be detected inductively, and still result in high-resolution NMR spectra. Rugar et al. (11) have shown that the mechanical detection schemes proposed by Sidles (12) can significantly reduce the LODs for both electron paramagnetic resonance and NMR. However, due to the inhomogeneous nature of the magnetic field, high-resolution spectroscopy is not yet possible with this technique. Wu et al. (13) used a number of solenoidal microcoils with diameters in the range 355 to 695 mm diameter for both static and dynamic NMR measurements, but only achieved linewidths on the order of 7–10 Hz. The most successful results so far have been obtained by Olson et al. (14), who showed that a solenoidal microcoil (355 mm diameter) increases the mass sensitivity by more than two orders of magnitude when compared with a standard 5 mm probe. High spectral resolution was achieved via a perfluorinated ‘‘susceptibility matching’’ fluid surrounding 83
AID
JMRB 7455
/
6o11$$$281
09-16-96 12:58:02
1064-1866/96 $18.00 Copyright q 1996 by Academic Press, Inc. All rights of reproduction in any form reserved.
magba
AP: Mag Res, Series B
84
COMMUNICATIONS
FIG. 1. Printed-circuit-board layout for positioning the microcoils at the center of the magnet. The fixed matching capacitor (Cm1 ) typically has a value between 1.5 and 2.5 pF. The variable tuning (Ct ) and matching capacitors (Cm2 ) have a range of 1–30 pF.
final turn, and this end was then reglued with permanent adhesive. Using the printed-circuit-board layout shown in Fig. 1, the capillary was centered between the two shoulders. The capillary was glued to the shoulders using permanent adhesive. The wire ends of the coil were soldered to the core and outer casing of the low-magnetic rigid coaxial cable (UT85SS, Rosenberger Micro-coax, Collegeville, Pennsylvania). The connections then were verified using a digital multimeter. A low-density polyethylene bottle was cut and epoxied to the circuit board to allow the coil to be submerged completely in the fluorinert. To tune and match the coil, nonmagnetic fixed (100B2R2PN, American Technical Ceramics, Huntington Station, New York) and variable (Johansen 5641, Boonton, New Jersey) capacitors were used. A fixed matching capacitor (in the range 1.5 to 2.5 pF) was soldered between the rigid coaxial core and the input terminal. Previous work (14) showed that LODs as low as 20 pmol can be achieved by using such solenoidal microcoils. However, the high spectral resolution was accompanied by a very small coil filling factor (approximately 4.4%) for a 355 mm outer diameter (o.d.) and 75 mm inner diameter (i.d.). In order to increase the filling factor, the thickness of the capillary wall must be reduced, meaning that the sample comes closer to the copper windings and the effects of magnetic susceptibility mismatches become more pronounced. To quantify this trade-off between sensitivity and resolution, we constructed a series of coils based on a 355 mm o.d. capillary, but varied the i.d. to alter the filling factor. Seventeen turns were used for all coils, with minimal spacing between the
AID
JMRB 7455
/
6o11$$$282
09-16-96 12:58:02
turns, resulting in a length of approximately 1.1 mm. Eighteen coils in all were tested. Electrical characterization of the coils was performed using a 1–500 MHz network analyzer (Hewlett–Packard, HP 8751). Having calibrated the system to remove the effects of the connecting cable, the coil was tuned to 250 MHz ( f0 ), and the cable soldered directly to the terminals of the coil, bypassing the matching capacitors. The value of the frequencies ( f1 and f2 ) at which the real and reactive components were equal was determined using a Smith Chart. The Q values, Q Å f0 /( f2 0 f1 ) (16), for coils 355 mm in diameter were measured to be between 30 and 35 for every coil tested. It should also be noted that the tuning range of the microcoils was very large. For coils of 355 mm o.d., with one fixed 2 pF capacitor, a 1–30 pF variable matching capacitor, and a 1–30 pF variable tuning capacitor, the range over which the coil can be exactly matched to 50 V was 180–310 MHz. For coils at these dimensions, resistive losses should be coil- rather than sample-dominated, meaning that the coil Q, and therefore S/N, should not be reduced by the introduction of a lossy sample. To demonstrate this, the S11 parameter was measured for a coil of 350/250 mm o.d./i.d. Initially the coil was filled with deionized water, and then successively with 100 and 200 mM sodium chloride solutions. Figure 2 shows the respective plots of S11 versus frequency for each sample. It can be seen that f0 changed by less than 80 kHz for even a highly conducting sample, and the decrease in the loaded versus unloaded Q of the coil was minimal. All NMR experiments were carried out at 250 MHz, using a Tecmag (Houston, Texas) Libra console and 89 mm bore Oxford Instruments magnet (Model 2280). A sample of deionized water was injected into the coil through a short length of Teflon tubing (10). After pulse calibration, the sample was autoshimmed for approximately one hour. The value of the receiver gain was adjusted so that the signal from the solenoid coil with the largest filling factor did not saturate either the mixer stage or the analog-to-digital converter. A Miteq AU-1054 broadband low-noise (1.09 dB noise figure, 32 { 0.3 dB gain) preamplifier (Hauppauge, New York) was placed in front of the mixing stage. A 50 W broadband amplifier (American Microwave Technology, Model M3137, 200–500 MHz) drove the coil, producing an 800 ns 907 pulse at full power for the 355 mm coils. For all spectroscopy experiments, 20 dB transmitter attenuation was introduced, resulting in a 907 pulse of approximately 10 ms. Two experiments were performed to check that radiation damping was not a contributing factor to the measurements: first, varying the tip angle from 57 to 907 resulted in no shift in the resonant frequency of the water peak; second, the linewidth of the peak did not decrease upon coil detuning within the magnet. S/N data were obtained using a spectral width of 10 kHz, 8192 complex data points, a 907 tip angle, and four transients, with CYCLOPS phase cycling (17). The large value
magba
AP: Mag Res, Series B
85
COMMUNICATIONS
FIG. 2. S11 and resonant frequency ( f0 ) for different loading of a 350/250 mm microcoil. (a) Deionized water, S11 Å 041.8 dB, f0 Å 249.95 MHz; (b) 100 mM saline, S11 Å 036.2 dB, f0 Å 249.90 MHz; and (c) 200 m M saline, S11 Å 034.9 dB, f0 Å 249.88 MHz.
of the spectral width was used to avoid baseline artifacts. Data were baseline corrected and Fourier transformed with no apodization. The ratio of the integrated signal intensity of the water peak to the root-mean-square (rms) noise was then calculated. Linewidth measurements were made using a frequency-domain Lorentzian line-fitting algorithm. The spectral width was set at 1000 Hz, with 16,384 complex data points acquired. Four transients were collected, again with CYCLOPS phase cycling. No apodization of the timedomain signal was used. The value of the linewidth reported in Table 1 was the full width at half-maximum (FWHM) of the fitted Lorentzian curve. Three coils were constructed for each inner diameter, and the standard deviation of the linewidth is reported. The data in Table 1 show that for a microcoil with outer diameter 355 mm, the filling factor can be significantly increased from the 4.4% reported previously to 28% with little loss in spectral resolution. A further increase to over 50% significantly increases the linewidth. It should be noted that
AID
JMRB 7455
/
6o11$$$282
09-16-96 12:58:02
the measurements were made on an older magnet than that in Ref. (14), which probably explains the slightly lower resolution obtained using an identical 4.4% filling factor coil. The S/N increases approximately linearly with the filling factor, as would be expected, since end effects are relatively minor. Figure 3 shows spectra obtained from 50 mM
TABLE 1
o.d./i.d. (mm)
Wall thickness (mm)
Filling factor (%)
Relative SNR
355/50 355/75 347/103 354/148 355/180 350/250
152.5 140 122 103 88 50
2.0 4.4 8.8 17.5 28.0 51.0
1.0 2.1 4.1 8.4 13.1 22.3
magba
AP: Mag Res, Series B
LWavg (Hz)
LWmin (Hz)
{ { { { { {
1.1 0.8 1.1 1.0 1.1 3.0
1.2 1.0 1.3 1.1 1.3 3.2
0.3 0.3 0.2 0.3 0.3 0.4
86
COMMUNICATIONS
FIG. 3. Spectra from 50 mM sucrose in D2O. Spectral width {1000 Hz, 8192 complex data points, recycle delay 6 s, 256 scans. The spectra are baseline corrected, and 1 Hz line broadening is applied. (a) 355/75 mm (i.d./o.d.) microcoil, (b) 355/180 mm (i.d./o.d.) microcoil, and (c) 355/250 mm (i.d./o.d.) microcoil.
sucrose in D2O for three coils of different inner diameter. Both the expected increase in S/N and the increased broadening due to the susceptibility mismatch are clearly seen. In conclusion, we have shown that the S/N obtained using previously reported solenoidal microcoils can be increased significantly with little loss in spectral resolution, and therefore the concentration LODs can be reduced by almost an order of magnitude. Coils exhibiting the larger linewidths could find use in on-line coupled NMR detection methods such as liquid chromatography or capillary electrophoresis, where the linewidth is often flow-limited, or in applications where linewidths are naturally large. A number of approaches could be used to improve the lineshape for coils with even larger filling factors. The susceptibility mismatch could be reduced by doping the fused silica capillary such that its susceptibility matches that of the sample. ‘‘Zerosusceptibility’’ wire could also be used, where the diamagnetic susceptibility of copper is canceled out by a paramagnetic material such as rhodium (18) or aluminum (19). This approach was relatively easy at a large scale, but obtaining precise and reproducible doping at small wire diameters remains to be demonstrated.
AID
JMRB 7455
/
6o11$$$282
09-16-96 12:58:02
ACKNOWLEDGMENTS This work was supported by a grant from the National Institutes of Health (PHS 1 RO1 GM53030-01). We acknowledge the assistance and technical support of Drs. Richard Magin (Magnetic Resonance Engineering Laboratory), Timothy Peck (Magnetic Resonance Microsensors Corp.), and Jonathan Sweedler and Dean Olson (School of Chemical Sciences).
REFERENCES 1. C. L. Putzig, Anal. Chem. 66, 26R (1994). 2. O. Vorm, P. Roepstorff, and M. Mann, Anal. Chem. 66, 3281 (1994). 3. A. L. Burlingame, R. K. Boyd, and S. J. Gaskell, Anal. Chem. 66, 634R (1994). 4. A. E. Derome, ‘‘Modern NMR Techniques for Chemistry Research,’’ p. 129, Pergamon Press, New York, 1987. 5. T. M. Barbara, J. Magn. Reson. A 109, 265 (1994). 6. J. S. Schoeniger and S. J. Blackband, J. Magn. Reson. B 104, 127 (1994). 7. Z. H. Cho, C. B. Ahn, S. C. Juh et al., Med. Phys. 15(6), 815 (1988). 8. E. W. McFarland and A. Mortara, Magn. Reson. Imaging 10, 279 (1992). 9. R. W. Wiseman, T. S. Moerland, and J. J. Kushmerik, NMR Biomed. 6, 153 (1993).
magba
AP: Mag Res, Series B
87
COMMUNICATIONS 10. E. Odeblad, ‘‘Micro-NMR in High Permanent Magnetic Fields,’’ Nordisk Forening for Obsterik och Gynekologi, Lund, Sweden, 1966. 11. D. Rugar, O. Zuger, S. Hoen, C. S. Yannoni, H-M. Vieth, and R. D. Kendrick, Science 264, 1560 (1994).
15. T. L. Peck, R. L. Magin, and P. C. Lauterbur, J. Magn. Reson. B 108, 114 (1995). 16. Application Note 154, Hewlett–Packard Co., Palo Alto, California, 1972.
12. J. A. Sidles, Appl. Phys. Lett. 58, 2854 (1991).
17. D. I. Hoult and R. E. Richards, Proc. R. Soc. London Ser. A 344, 311 (1975).
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AID
JMRB 7455
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6o11$$$282
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magba
AP: Mag Res, Series B