WITHDRAWN: 3D-printed RF probeheads for low-cost, high-throughput NMR

    3D-printed RF probeheads for low-cost, high-throughput NMR R. Adam Horch, John C. Gore PII: DOI: Reference:

S0730-725X(17)30004-8 doi:10.1016/j.mri.2017.01.005 MRI 8712

To appear in:

Magnetic Resonance Imaging

Received date: Accepted date:

4 January 2017 6 January 2017

Please cite this article as: Horch R. Adam, Gore John C., 3D-printed RF probeheads for low-cost, high-throughput NMR, Magnetic Resonance Imaging (2017), doi:10.1016/j.mri.2017.01.005

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Technical Note

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3D-printed RF Probeheads for Low-cost, High-throughput NMR

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R. Adam Horch1,2 and John C. Gore1,2 1

Vanderbilt University Institute of Imaging Science, Nashville, TN, USA

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John C. Gore

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Corresponding Author:

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Department of Radiology & Radiological Sciences, Vanderbilt University, Nashville, TN, USA

Vanderbilt University Institute of Imaging Science 1161 21st Ave South Nashville TN, 37232

[email protected] 615 322 8359

ACCEPTED MANUSCRIPT Abstract 3D printing has been exploited as a means to fabricate complete NMR probeheads containing arrays of miniature RF circuits for high-throughput solution-state NMR spectroscopy and potentially other purposes. 3D-printed NMR circuits of

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millimeter scale were constructed consisting of RF coils, variable tuning/matching capacitors, and liquid NMR sample cavities. Channels and cavities capable of being addressed using microfluidics are included in the probehead structure,

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providing a means for hydraulically-controlled RF tuning/matching and liquid NMR sample loading/unloading.

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Electrically conductive RF circuitry is defined within the 3D-printed polymer bodies by metallizing relevant channels and structures with silver. The unique properties of 3D printing enable facile construction of potentially thousands of coils at

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low cost, giving way to dense coil arrays for high-throughput NMR and novel coil geometries.

ACCEPTED MANUSCRIPT Introduction Conventional probeheads for solution-state NMR are usually constructed using manual1 or photolithographic techniques2 that incorporate RF coils, tune/match circuitry, and liquid sample holders into spatially-compact housings. These

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techniques are suitable for constructing arrays of probes with up to a few 10s of RF coils but the products are expensive, time consuming, and labor-intensive to manufacture. As an alternative, we have been exploring stereographic 3D printing

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that provides rapid, low-cost fabrication with minimal geometric constraints. 3D printing allows the creation of

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topologically complex structures in a wide variety of NMR-compatible polymers, with print resolutions of ~10µm across large volumes. We here demonstrate the feasibility of designing and manufacturing complete, 3D-printed NMR

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probeheads that contain RF resonators, variable tuning/matching capacitors, and liquid NMR sample cavities. The

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probehead structure also incorporates microfluidically-addressable channels and cavities that provide a means for hydraulic control of RF tuning/matching and liquid NMR sample loading/unloading. Electrically conductive RF circuitry is defined within the 3D printed polymer bodies by metallizing certain structures with silver. In this way, multiple

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independent RF coils and NMR sample cavities can be fabricated into a single probehead for high-throughput NMR. The unique scalability of 3D printing supports fabricating hundreds of millimeter-scale coils in a single build, potentially

Methods

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providing a manufacturing pathway towards a new generation of low-cost, high-throughput probeheads.

Stereographic 3D printing uses liquid polymer resins that are photo-crosslinked by a laser in a layer-by-layer manner. With a 3D Systems iPro 9000XL Printer using the Somos 11122 Watershed material (DSM Desotech), probeheads were formed with an in-layer resolution of 40 µm and a through-layer resolution of 150 µm. Probeheads were printed with a number of non-connecting hollow channels, defining RF circuitry, hydraulic control lines for variable capacitors, or NMR sample loading pathways. After printing, the RF circuit channels were selectively metallized by injecting PELCO Silver Paint (Ted Pella Inc., Redding, CA) to form ≈10µm silver coatings to create electrically conductive pathways. In this way, RF-resonant solenoids were constructed and tuned/matched using parallel-plate variable capacitor networks included in the probehead. These capacitors contained a partially hollowed dielectric (Figure 1), which was filled with a variable amount of Fomblin fluorocarbon oil (Solvay Solexis Inc., West Deptford, NTo test performance,) or D2O (99.9%, SigmaAldrich Inc., St. Louis, MO). Fomblin and D2O are immiscible and have dielectric constants that differ by 40-fold, so a

ACCEPTED MANUSCRIPT moveable liquid interface between the two was placed within the capacitor’s dielectric gap to provide hydraulic control of net capacitance. Additionally, Fomblin and D2O are invisible to 1H NMR and bear similar magnetic susceptibility to H2O, thus allowing the parallel plate capacitors to be placed in the vicinity of the NMR sample for a compact RF coil footprint. To test the performance, probehead sample chambers were filled with 40 µL sa, and 1H FIDs were collected on a 9.4T

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Varian/Agilent small animal imaging system (10kHz BW, 40,000 points, 1 acquisition).

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Results

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Probes were successfully printed with 0.75mm-diameter hollow channels to define RF coils, each consisting of a 5mmdiameter/5-turn solenoid and three parallel-plate capacitors for tuning/matching (Figure 2). The complete RF coil circuit

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occupied a 2 mL footprint, which was printed into an 8mL probehead body with fluid couplings for separate hydraulic control of the capacitors and NMR sample (Figure 3). RF bench testing showed a broad tuning range of 40 MHz as the

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capacitors were hydraulically varied, with Q ≈ 15 at 400 MHz (Figure 4). A match of only -12dB (S11) could be achieved

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at 400 MHz, and further efforts could improve the coil geometry and capacitor range for an improved match. However, 1H FIDs from 40 µL saline were observed at 400 MHz (Figure 5), with a signal to noise ratio ≈ 20,000 and ≈ 20 Hz linewidth

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acceptable for high-throughput NMR processes such as drug screening. The coil gave a 1 kHz nutation rate under 125 mW input RF power, indicating compatibility with low-cost, low-power RF front-end electronics.

Discussion and Conclusions

3D printing and selective silvering has been demonstrated as a new means to fabricate complete NMR probeheads for solution-state NMR. Importantly, RF coil tuning/matching and NMR sample loading/unloading may both be controlled hydraulically, which is compatible with high-throughput technologies commonly used within the microfluidics industry. Entire coil arrays may be built with densities greater than 1 coil per mL. Recently-developed 3D printers have driven the minimum build resolutions to 5-fold smaller than what was used herein, so single probeheads with high-density arrays of independent RF coils and NMR sample pathways are clearly feasible. Ultimately, the metallizing process may be combined with the 3D-printing process for facile construction of large numbers of coils. Given its low cost and build scalability, 3D printing offers a unique means to construct probeheads of unprecedented complexity, enabling drastically

ACCEPTED MANUSCRIPT denser arrays for high-throughput NMR and novel coil geometries that are not available with conventional fabrication techniques.

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References 1) Webb, A. G. Progress in Nuclear Magnetic Resonance Spectroscopy 31, 1–42 (1997)

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2) Lee H, Sun E, Ham D, Weissleder R. Chip-NMR biosensor for detection and molecular analysis of cells. Nat Med.

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2008;14(8):869-74

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Acknowledgements

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This work was supported by a grant from the National Institutes of Health (Grant T32EB001628 awarded to JCG).

ACCEPTED MANUSCRIPT Figure 1: Schematic of 3D-printed, parallel-plate variable capacitor for hydraulic tuning. Two conductive plates (left) span a dielectric gap consisting of two 3D-printed matrix layers (thickness dM) and a hollow hydraulic layer filled with Fomblin or D2O (thickness dH). The immiscible Fomblin/D2O interface can be moved across the capacitor via hydraulic pressure, varying total capacitance by way of their 40-fold-different dielectric constant (K). An equivalent electrical

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schematic is shown at right.

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Figure 2: Probehead electrical schematic and physical layout. A conventional RF resonant circuit was used (upper left), consisting of three variable capacitors for matching/tuning/balancing and a solenoid for sensing the NMR sample. This

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circuit was implemented via 3D-printed hollow structures (shown as solid bodies in various color-coded views), which were rendered in a non-conductive solid polymer body. Electrically-conductive channels defining the RF circuit (red,

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purple, yellow) were selectively metallized, while hydraulic capacitor control lines (green) and NMR sample lines (blue)

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remained unaltered.

Figure 3: Representative photographs of prototype 3D-printed probehead. The complete probehead with RF transmission

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line and hydraulic/sample fluid lines is shown at left. Luer lock interfaces adapted the probehead fluid channels to eight 1mL syringes. A close-up schematic view of the probehead core is shown at upper-right (color-coded to Figure 2), above corresponding photographs of the probehead body before and after metallization with silver ink using a number of fill ports.

Figure 4: Network analyzer S11 sweep. Probehead S11 response (400MHz center, 400MHz span) is shown before (top) and after (bottom) the tuning capacitor is varied hydraulically by injection of D2O. In the presence of a 40 µL saline load, the best observed match was -12dBm at 400 MHz with a Q of ~15.

Figure 5: Representative 1H NMR spectrum. A single resonance was observed from a saline load, with shoulders likely arising from a difference between sample and probehead magnetic susceptibility. A narrow, unshimmed linewidth is conducive to high-throughput probeheads which contain multiple coils that may not be individually-shimmed.

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ACCEPTED MANUSCRIPT Highlights 3D printing has been exploited as a new means to fabricate arrays of RF probes for high-throughput solution-state NMR. 3D-printed probes of millimeter scale were constructed consisting of RF resonators, variable tuning/matching capacitors,

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and liquid NMR sample cavities. Fluidically-addressable channels and cavities provide a means for hydraulically-

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defined within the 3D printed bodies by metallizing with silver ink.

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controlled RF tuning/matching and liquid NMR sample loading/unloading, while electrically conductive elements are