Nuclear magnetic resonance flow probe and method of operating and manufacturing the same

Abstract

A nuclear magnetic resonance (NMR) flow probe includes an elongated probe body, a first coil, a second coil, and a switch circuit. The probe body has an inlet and an outlet and is configured to receive a flow of a fluid between the inlet and the outlet. The first coil is disposed around the probe body and is configured to transmit radio frequency radiation to the fluid in the probe body. The second coil is disposed around the probe body and is configured to receive radio frequency radiation emitted by the fluid in the probe body. The switch circuit is configured to control the first and second coils.

Description

NUCLEAR MAGNETIC RESONANCE FLOW PROBE AND METHOD OF OPERATING AND MANUFACTURING THE SAMECROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 63 / 666,379, filed July 1, 2024, which is incorporated by reference in its entirety herein.TECHNICAL FIELD

[0002] The present disclosure relates broadly to nuclear magnetic resonance (NMR) spectroscopy or relaxometry for bioprocess and chemical reaction monitoring, and more particularly, to an NMR flow probe and method of operating and manufacturing the same.BACKGROUND

[0003] NMR spectrometry and relaxometry can provide valuable monitoring of chemical reactions, bioreactor development, and the manufacturing of pharmaceuticals and foods. Current NMR measurements are largely limited to static samples because these measurements often require observation of an excited nuclear magnetization over several seconds, and moving fluids with high flow rates may push the excited portion of the fluid out of the measurement coil during the experiment. As an example, to adequately capture the approximately two-second relaxation of bioreactor media at low cell densities, the echo train should be at least four or five seconds long. At the flow rates used in some perfusion bioreactors, the entire sample may have left the coil in a fraction of this time, resulting in an erroneously short measured T2 time and a nonexponential decay that is difficult to process. At sufficiently high flow rates, this becomes a limiting factor for NMR experiments as well, causing broadened line width and lower sensitivity.

[0004] Additionally, it is generally necessary to wait several times the T1 relaxation time in between scans in an NMR experiment to allow the sample to decay. Replacing the sample with another, identical sample can reduce the inter-experiment delay to speed up experiments. For carbon-13 nuclear magnetic resonance (13C NMR), this can reduce the inter-experiment delay from nearly a minute for a full 90-degree excitation down to hundreds of milliseconds. This is crucial for high-resolution NMR where experiments often involve many thousands of scans. However, the effects of flow on the NMR signalacquisition for moving samples, or the additional complexity of a pump to start and stop the flow can make this difficult to realize in most cases.

[0005] This is a significant problem for many systems that perform NMR measurements on moving samples, and several workarounds have been proposed. For flow NMR applications, the effect of a moving sample is typically corrected mathematically by including the depletion of the magnetized sample as a relaxation term that can be calibrated out by comparing the scans with scans from stationary samples. This is typically effective for low, constant flow rates and short experiments, but not for longer experiments like Carr-Purcell-Meiboom-Gill (CPMG) sequence or for pulsating flow such as that caused by peristaltic pumps. Even with proper calibration, different relaxation times associated with different nuclei in NMR can cause the effects of flow to be different between different peaks in the same scan. Furthermore, drag caused by the walls of the tube cause samples with even perfectly laminar flow to “smear” in ways that makes complete mathematical compensation infeasible. These problems can be partially addressed by increasing the coil cross sectional area to lower the flow velocity through the coil, but this approach is limited by the magnet size and not suitable for some cell samples that need high flow rates to stay suspended. Some conventional approaches settle for lower flow rates to limit the effect of sample depletion, a compromise that constrains integration with existing processes where the flow velocity is set by other parts of the system. Yet another conventional approach uses a low-pulsation pump to maintain a carefully controlled and very consistent flow rate through the probe, which adds more complexity and further limits the flexibility of the measurement.

[0006] It may be desirable to provide methods and devices that can address at least some of the above problems.SUMMARY

[0007] According to an aspect of the present disclosure, there is provided a nuclear magnetic resonance (NMR) flow probe comprising an elongated probe body having an inlet and an outlet and configured to receive a flow of a fluid between the inlet and the outlet; a first coil disposed around the probe body and configured to transmit radio frequency radiation to the fluid in the probe body; a second coil disposed around the probe body and configuredto receive radio frequency radiation emitted by the fluid in the probe body; and a switch circuit configured to control the first and second coils.

[0008] In one embodiment, the first and second coils may be disposed around the same part of the probe body such that the second coil forms an inner coil and the first coil forms an outer coil. The switch circuit may be configured to alternately switch on the first and second coils for magnetically decoupling the first and second coils. The switch circuit may comprise at least one radio frequency switch or limiter circuit.

[0009] In another embodiment, the first coil may be disposed around substantially a whole length of the probe body and the second coil may be disposed around a part of the probe body proximate to the outlet. The second coil comprises a portion of the first coil. The switch circuit may be configured to simultaneously switch on both the first and second coils for a transmit pulse. The switch circuit may comprise a solid-state switch.

[0010] According to another aspect of the present disclosure, there is provided a method of operating a nuclear magnetic resonance (NMR) flow probe, the method comprising providing the NMR flow probe as described; connecting the first coil to a transmitter; connecting the second coil to a receiver; providing the flow of fluid through the probe body; and operating the switch circuit to control transmission of radio frequency radiation to the fluid in the probe body and reception of radio frequency radiation emitted by the fluid in the probe body.

[0011] A method of manufacturing a nuclear magnetic resonance (NMR) flow probe, the method comprising: providing an elongated probe body having an inlet and an outlet, wherein the probe body is configured to receive a flow of a fluid between the inlet and the outlet; disposing a first coil around the probe body, wherein the first coil is configured to transmit radio frequency radiation to the fluid in the probe body; disposing a second coil disposed around the probe body, wherein the second coil is configured to receive radio frequency radiation emitted by the fluid in the probe body; and connecting a switch circuit to the first and second coils for controlling the first and second coils.

[0012] The first and second coils may be disposed around the same part of the probe body such that the second coil forms an inner coil and the first coil forms an outer coil.

[0013] The switch circuit may be connected such that the switch circuit alternately switches on the first and second coils for magnetically decoupling the first and second coils.

[0014] The switch circuit may comprise at least one radio frequency switch or limiter circuit.

[0015] The first coil may be disposed around substantially a whole length of the probe body and the second coil may be disposed around a part of the probe body proximate to the outlet. The second coil comprises a portion of the first coil.

[0016] The switch circuit may be connected such that the switch circuit simultaneously switches on both the first and second coils for a transmit pulse.

[0017] The switch circuit may comprise a solid-state switch.BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Embodiments of the disclosure will be better understood and readily apparent to one of ordinary skill in the art from the following written description, by way of example only, and in conjunction with the drawings, in which:

[0019] Fig. 1 shows a photograph of a prototype of the NMR flow probe according to one embodiment.

[0020] Figs. 2A-2C show schematic diagrams illustrating an NMR flow probe according to another embodiment.

[0021] Fig. 3 shows a circuit diagram of a switch circuit used with the NMR flow probe of Fig. 2.

[0022] Figs. 4A and 4B show photographs of example prototypes of the NMR flow probe of Fig. 2.

[0023] Fig. 5A shows an arrangement of the tubing and the NMR flow probe according to the present disclosure within a magnet and temperature control system.

[0024] Fig. 5B shows a photograph of the probe assembly of Fig. 5 A.

[0025] Fig. 6 shows graphs illustrating performance of the NMR flow probe of Fig. 2 at different flow rates.

[0026] Fig. 7 shows a flow chart illustrating a method for manufacturing an NMR flow probe according to an example embodiment.

[0027] Skilled artisans will appreciate that elements in the figures are illustrated for simplicity and clarity and have not necessarily been depicted to scale. For example, the dimensions of some of the elements in the illustrations, block diagrams or flowcharts may be exaggerated in respect to other elements to help to improve understanding of the present embodiments.DETAILED DESCRIPTION

[0028] The present disclosure provides coil geometries for a flow probe that can be used to perform NMR experiments on rapidly moving fluids. Provided that the maximum flow velocity within the sample is bound, the signal from relaxometry or NMR experiment can match that for static samples. This can make it possible to use MR relaxometry and spectrometry to monitor high flow velocity processes and samples that flow at variable rates without knowing the instantaneous flow rate at every point in time during the experiment.

[0029] According to example embodiments, a separate transmit coil is used to excite and refocus a much larger sample volume. The coil designs according to the present disclosure can eliminate the effect of fluid movement on the signal from the sample, so that long relaxation experiments can be performed on fast moving fluids or fluids with a complicated, pulsating flow such as that created by peristaltic pumps.

[0030] The present disclosure also provides an NMR flow probe that includes a probe body, a first coil, a second coil and a switch circuit. The probe body includes an inlet and an outlet and is configured to receive a flow of a fluid between the inlet and the outlet. The first coil is disposed around the probe body and is configured to transmit radio frequency radiation to the fluid in the probe body. The second coil is disposed around theprobe body and is configured to receive radio frequency radiation emitted by the fluid in the probe body. The switch circuit is configured to control the first and second coils.

[0031] Embodiments will be described, by way of example only, with reference to the drawings. Like reference numerals and characters in the drawings refer to like elements or equivalents.

[0032] In a first embodiment, the receive coil lies within the outer transmit coil, and needs to be switched open during transmit pulse so that the two coils do not couple. Fig. 1 shows a photograph of a prototype NMR flow cell assembly 100 according to the first embodiment. Here, the first coil (i.e. the outer coil 102) is wound around the second coil (e.g. a bobbin 104) that slides over the probe body which is in the form of an NMR tube 106. A printed circuit board 108 includes the switch circuit 110 for controlling the coils 102, 104. In use, the assembly 100 can be autoclaved with the bioreactor tubing, and then snapped into a receiving circuit with the tuning and matching capacitors (not shown). The large size of the transmit coil (i.e. the outer coil 102), and the strong coupling between the two coils 102, 104 may make the probe susceptible to electric field noise, so shielding of the whole probe assembly is also provided. The transmitter and receiver are connected to the outer and inner coils respectively. Further, a radio frequency (RF) switch may be used to blank the transmitter during the receive window, since any noise from the power amplifier may couple into the receiver. The receiver amplifiers can be protected from the transmitter using either a limiter circuit or another RF switch.

[0033] In a second embodiment, a coil can be tapped near the outlet side, so that only a small portion near the outlet side is used for detection. The coil needs to be switched so that the entire coil is used for the transmit pulse. That is, a single long solenoid is used for transmission, and a small portion of this solenoid is disconnected and used alone for reception. Notably, the transmit sections of each coil configuration do not need to be highly resonant, allowing for the use of longer solenoids with low self-resonance frequencies that would not be suitable for reception. For this reason, the maximum transmit coil length (which determines the maximum flow velocity that the system can accommodate) is limited only by the properties of the external magnet and not by the required radiofrequency properties of the receiver.

[0034] Fig. 2A shows a schematic diagram illustrating an NMR flow probe 200 according to the second embodiment. The NMR flow probe 200 uses the split coil approach in which the first coil (e.g. transmit coil 202) is disposed around substantially a whole length of the probe body 206 and the second coil (e.g. receive coil 204) is disposed around a part of the probe body 206 proximate to the outlet.

[0035] In other words, a smaller receive coil on the “outlet” side of the larger coil sees only fluid that has been within the homogeneous region of the larger coil for the entire duration of the experiment, so the signal in the receive coil is not dependent on flow velocity. This is true even for the pulsed flow created by peristaltic pumps as long as the average flow rate does push fluid all the way through the transmit coil. Figs. 2B and 2C illustrate the working principle of the NMR flow probe of Fig. 2A. When the experiment starts, a large volume of sample is excited by a long transmit coil 202. As the experiment progresses, some of the sample flows out of the transmit coil 202 and is lost, and new sample that has not been excited flows into the transmit coil 202. If the flow rate is sufficiently low such that only sample that has spent the entire duration of the experiment within the transmit coil 202 flows through the receive coil, the received signal will be insensitive to the flow rate. As can be seen in Fig. 2B, when 90-degree pulse is applied, the fluid particles in the probe body 206 are excited by the transmit coil 202 before reaching the receive coil 204 where the emitted signal is detected. Further, as can be seen in Fig. 2C, when a CPMG pulse sequence is applied, there are different flow regions in the probe body 206, including a region 208 where the fluid particles not excited, a region 210 where the fluid particles are excited, and a region 212 where the fluid particles are not refocused. The regions 208 and 210 are between the transmit coil 202 and receive coil 204, while region 212 is downstream of the receive coil 204.

[0036] Fig. 3 shows a circuit diagram of a switch circuit 300 used with the NMR flow probe of Fig. 2. In Fig. 3, the longer portion of the coil (i.e. transmit section 302) is shown at the top, while the receive section 304 of the coil is in the center bottom. The switch 306 needs to be part of the tuned circuit. As discussed above, the switch circuit 300 is configured to simultaneously switch on both the first and second coils (i.e. transmit section 302 and receive section 304) for a transmit pulse. Figs. 4A and 4B shows photographs of example prototypes of the NMR flow probe 200 of Fig. 2. In the prototype of Fig. 4A, the coil is wound with 22-gauge magnet wire around 3D printed bobbins to produce coilsthat are 22 mm long. The receive section of the coil is 5 mm long. This is large enough that a high signal-to-noise ratio is achievable but not so large that the self-resonance frequency of the receive coil falls below the Larmor frequency of the magnet. The bobbin includes a clip that keeps the lead of the transmit-only section as close as possible to the adjacent lead to the receive section to minimize distortion in the field generated by the solenoid near this junction. In the prototype of Fig. 4B, three coaxial cables 402, 404, 406 allow the switch to be located outside of the magnet so that reed relays can be used for simplicity. At scale, this may be a solid-state diode switch, e.g. a PIN diode switch, built into the coil tuning circuit. The transmit only section and fluid inlet are at the top in Figs. 4A and 4B.

[0037] In a non-limiting example, the tubing used in the bioreactors has an inner diameter of 3.2mm, and is typically operated at a flow rate of 7mL / min. The inner diameter is sufficiently close to the 4.2mm inner diameter of a high throughput 5mm NMR tube such that the change in flow rates may not cause the cells to fall out of suspension, so the tubing is used as the only wetted component and the form for the inner coil. The required length of the outer coil for a given flow rate and cross-sectional area is given by I = rt / A where r is flow rate in m3 / s, t is the experiment duration, and A is the tubing cross sectional area in m2. For the 7mL / min flow rate through the NMR tube, the flow velocity is 8.4mm / s, so a 5cm long coil is sufficient for a 6-second-long experiment. The length of the receive coil is also added to the length of the transmit coil, along with enough additional length to move the fringe fields from the edge of the solenoid out of the volume of interest. Finally, the moving fluid needs to experience the applied magnetic field B0 for several Tls to become polarized. In on implementation, this is done by folding the inlet tube back and forth within the magnet.

[0038] Using the prototype of Fig. 4 A, the coil is mounted on FR4 printed circuit board probes, which include shielded traces that connect the leads from the coil to the switching and tuning circuits, which are located outside of the magnet to avoid any impact on the magnetic field homogeneity due to variations in permeability in the solder or other components. This makes it possible to use reed relays to switch the coils rather than solid-state switches, which may simplify the tuning and matching of the coils at the cost of a long minimum echo time in order to allow the relays to switch completely. Theadditional length added between the transmit-only and receive sections of the coil required to move the switching and tuning circuits out of the magnet is around 250 mm, which is short enough that the phase shift it creates between the parts of the coil is negligible at the 20 MHz Larmor frequency of the permanent magnet used.

[0039] The coil is positioned within a 0.5T model 3 NMR Permanent Magnet (SpinCore Technologies Inc., USA) with a pole face spacing of 0.75 in. and a homogeneity of about 100 ppm. It is housed within an aluminum enclosure and a layer of 1 in. thick insulating foam to isolate it from variations in the room temperature. The temperature of the magnet itself is controlled to within 0.007 °C to prevent the resonant frequency from drifting during experiments.

[0040] Fig. 5A shows an arrangement of the tubing and the present NMR flow probe within a magnet and temperature control system. In Fig. 5A, the static field B0 is oriented out of the page. The inlet side of the tubing is wound back and forth within the magnet so that the incoming fluid can become polarized before entering the coil. The coils and switching / tuning / matching circuitry are supported by a printed circuit board that protrudes into the magnet. Fig. 5B shows a photograph of the probe assembly after it is removed from the magnet.

[0041] To evaluate the continuous flow probe, a CPMG experiment has been run on the split coil flow probe as described above with reference to Figs. 2-5, with tubing connected to a syringe pump primed with water. In each experiment, the curves from the flow probe with a stationary sample (e.g. line 602 in Fig. 6) are compared to the curves from the flow probe with moving samples (e.g. line 604 in Fig. 6) and also with only the receive section of the coil connected (e.g. line 606 in Fig. 6). When the transmit section of the flow probe is not used, the data it collects shows the signal that would be available to a conventional probe.

[0042] To confirm that the coil behaves as expected, the flow rate of the water is increased above the maximum rate supported by the flow probe in the second and third experiments. When the unexcited water that started the experiment outside of the transmit coil enters the receive section of the coil, a strong decrease in the signal can be observed. In other words, the effect of the sample movement is significantly reduced.Until the unexcited fluid reaches the receive coil, the received signal from a moving fluid will match the signal from the same sample if it were stationary. Fig. 6 shows results from the flow probe at 2ml / min, 4ml / min, and lOml / min flow rates. Flow suppression is observed until the unexcited fluid reaches the receive section of the coil.

[0043] The flow probe according to the embodiments of the present disclosure is especially useful for bioprocess monitoring with magnetic relaxometry, where high flow rates and true continuous monitoring are desirable but long CPMG experiments are required for accurate relaxation time measurements. The flow probe enables cell density measurements on perfusion bioreactors without an additional pump or branch in the system, thereby reducing complexity and improving reliability. This technology would also allow the process monitoring applications to be flow-rate agnostic. Liquid Chromatography-Nuclear Magnetic Resonance (LC-NMR) may also be enhanced with a coil geometry that is flow rate agnostic, since slowing the moving sample down increases peak broadening due to diffusion. Stop-flow systems, where the stream is halted during each sample, are inherently limited in their temporal resolution, whereas a flow probe that is designed to be depleted at the end of the receive window for each scan allows a spectrometer to run continuously. For most basic NMR experiments, the approach that combines the advantages of moving samples that avoid having to wait for the magnetization to reset and stationary samples that avoid artificial relaxation gives the maximum possible signal to noise ratio in the smallest amount of time. Furthermore, the flow probe of the present disclosure makes it possible to run many NMR experiments designed for stationary samples on moving samples without regard to the flow characteristics, provided that the maximum average flow rate is not exceeded during the experiment. This translates directly to the high field / precision NMR applications.

[0044] Fig. 7 shows a flow chart 700 illustrating a method for manufacturing an NMR flow probe according to an example embodiment. At step 702, a probe body having an inlet and an outlet is provided. The probe body is configured to receive a flow of a fluid between the inlet and the outlet. At step 704, a first coil is disposed around the probe body. The first coil is configured to transmit radio frequency radiation to the fluid in the probe body. At step 706, a second coil is disposed around the probe body. The second coil is configured to receive radio frequency radiation emitted by the fluid in the probe body. At step708, a switch circuit is connected to the first and second coils for controlling the first and second coils.

[0045] It will be appreciated by a person skilled in the art that numerous variations and / or modifications may be made to the present disclosure as shown in the specific embodiments without departing from the scope of the disclosure as broadly described. The present embodiments are, therefore, to be considered in all respects to be illustrative and not restrictive.References:[1] M. B. Taraban et al., “Analysis of the Adsorbed Vaccine Formulations Using Water Proton Nuclear Magnetic Resonance-Comparison with Optical Analytics,” Pharm. Res., vol. 40, no. 8, pp. 1989-1998, Aug. 2023, doi: 10.1007 / sl 1095-023-03528-7.[2] M. B. Taraban, Y. Wang, K. T. Briggs, and Y. B. Yu, “Inspecting Insulin Products Using Water Proton NMR. I. Noninvasive vs Invasive Inspection,” J. Diabetes Sci. Technol., vol. 16, no. 6, pp. 1410-1418, Nov. 2022, doi: 10.1177 / 19322968211023806.[3] M. B. Taraban et al., “Assessing Antigen-Adjuvant Complex Stability Against Physical Stresses By wNMR,” Pharm. Res., vol. 40, no. 6, pp. 1435-1446, Jun. 2023, doi: 10.1007 / s 11095-022-03437- 1.[4] K. T. Briggs, M. B. Taraban, and Y. B. Yu, “Quality assurance at the point-of-care: Noninvasively detecting vaccine freezing variability using water proton NMR,” Vaccine, vol. 38, no. 31, pp. 4853-4860, Jun. 2020, doi: 10.1016 / j.vaccine.2020.05.049.[5] W. K. Peng, U. Chen, B. O. Boehm, J. Han, and T. P. Uoh, “Molecular phenotyping of oxidative stress in diabetes mellitus with point-of-care NMR system,” Npj Aging Meeh. Dis., vol. 6, no. 1, Art. no. 1, Oct. 2020, doi: 10.1038 / s41514-020-00049-0.[6] S. S. Thamarath et al., “Rapid and Uive-cell Detection of Senescence in Mesenchymal Stem Cells by Micro Magnetic Resonance Relaxometry.” bioRxiv, p. 2022.06.01.494362, Jun. 02, 2022. doi: 10.1101 / 2022.06.01.494362.[7] J. Z. Y. Tan et al., “Label-free assessment of differentiation efficiency in iPSC- derived spinal cord progenitor cells via Magnetic Resonance Relaxometry (MRR),” 2022. Accessed: Feb. 18, 2024. [Online]. Available: https: / / dr.ntu.edu.sg / handleZl 0356 / 163335[8] D. Roxby, “Magnetic resonance relaxometry as a tool for tracking induced pluripotent stem cell variability,” presented at the TERMIS-AP 2022, Jeju, South Korea, Oct. 05, 2022. [Online]. Available: https: / / www.liebertpub.com / doi / 10.1089 / ten.tea.2022.29036.abstracts[9] K. Wachowicz and R. E. Snyder, “A continuous-flow perfusion system for the maintenance and NMR study of small tissue samples in vitro,” Magn. Reson. Mater. Phys. Biol. Med., vol. 18, no. 1, pp. 35-40, Mar. 2005, doi: 10.1007 / sl0334-004-0092-2.

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Claims

CLAIMS1. A nuclear magnetic resonance (NMR) flow probe comprising: an elongated probe body having an inlet and an outlet and configured to receive a flow of a fluid between the inlet and the outlet; a first coil disposed around the probe body and configured to transmit radio frequency radiation to the fluid in the probe body; a second coil disposed around the probe body and configured to receive radio frequency radiation emitted by the fluid in the probe body; and a switch circuit configured to control the first and second coils.

2. The NMR flow probe according to claim 1, wherein the first and second coils are disposed around the same part of the probe body such that the second coil forms an inner coil and the first coil forms an outer coil.

3. The NMR flow probe according to claim 2, wherein the switch circuit is configured to alternately switch on the first and second coils for magnetically decoupling the first and second coils.

4. The NMR flow probe according to claim 3, wherein the switch circuit comprises at least one radio frequency switch or limiter circuit.

5. The NMR flow probe according to claim 1, wherein the first coil is disposed around substantially a whole length of the probe body and the second coil is disposed around a part of the probe body proximate to the outlet.

6. The NMR flow probe according to claim 5, wherein the second coil comprises a portion of the first coil.

7. The NMR flow probe according to claim 5, wherein the switch circuit is configured to simultaneously switch on both the first and second coils for a transmit pulse.

8. The NMR flow probe according to claim 7, wherein the switch circuit comprises a solid-state switch.

9. A method of operating a nuclear magnetic resonance (NMR) flow probe, the method comprising: providing the NMR flow probe according to claim 1 ; connecting the first coil to a transmitter; connecting the second coil to a receiver; providing the flow of fluid through the probe body; and operating the switch circuit to control transmission of radio frequency radiation to the fluid in the probe body and reception of radio frequency radiation emitted by the fluid in the probe body.

10. A method of manufacturing a nuclear magnetic resonance (NMR) flow probe, the method comprising: providing an elongated probe body having an inlet and an outlet, wherein the probe body is configured to receive a flow of a fluid between the inlet and the outlet; disposing a first coil around the probe body, wherein the first coil is configured to transmit radio frequency radiation to the fluid in the probe body; disposing a second coil disposed around the probe body, wherein the second coil is configured to receive radio frequency radiation emitted by the fluid in the probe body; and connecting a switch circuit to the first and second coils for controlling the first and second coils.

11. The method according to claim 10, wherein the first and second coils are disposed around the same part of the probe body such that the second coil forms an inner coil and the first coil forms an outer coil.

12. The method according to claim 11, wherein the switch circuit is connected such that the switch circuit alternately switches on the first and second coils for magnetically decoupling the first and second coils.

13. The method according to claim 12, wherein the switch circuit comprises at least one radio frequency switch or limiter circuit.

14. The method according to claim 10, wherein the first coil is disposed around substantially a whole length of the probe body and the second coil is disposed around a part of the probe body proximate to the outlet.

15. The method according to claim 14, wherein the second coil comprises a portion of the first coil.

16. The method according to claim 14, wherein the switch circuit is connected such that the switch circuit simultaneously switches on both the first and second coils for a transmit pulse.

17. The method according to claim 16, wherein the switch circuit comprises a solid-state switch.

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