BIO-MEMS PLATFORM WITH INTEGRATED MICROFLUIDICS AND 3D MICRO-COILS FOR PARALLEL MRI AT MICROSCALE

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V. Badilita1*, K. Kratt1*, N. Baxan2, T. Burger1, R. Meier1, J. Hennig2, J.G. Korvink3,4, and U. Wallrabe1

Dept. of Microsystems Engineering – IMTEK, Microactuators Lab., Univ. of Freiburg, GERMANY 2 Dept. of Diagnostic Radiology, Medical Physics, Univ. Hospital Freiburg, GERMANY 3 Dept. of Microsystems Engineering – IMTEK, Simulation Lab., Univ. of Freiburg, GERMANY 4 Freiburg Institute for Advanced Studies – FRIAS, Univ. of Freiburg, GERMANY ABSTRACT We present for the first time high quality MR images taken with 3D geometrically perfect solenoidal micro-coils fabricated in a fully MEMS-integrated technology. We report MR images with an in-plane resolution of 10x10µm2 and a signal to noise ratio (SNR) – 47 for 5min scan time. MR images are acquired with tranceive micro-coils with 5 windings of insulated 25µm-diameter Au wire and with quality factors (Q) as high as 45. We report a process to integrate the 3D micro-coils into a Bio-MEMS platform for high-throughput cell level MRI by embedding in a polydimethylsiloxane (PDMS) scaffold with microfluidic channels and control valves for parallel probe handling. KEYWORDS: lab-on-a-chip, magnetic resonance imaging, 3D micro-coils INTRODUCTION As nuclear magnetic resonance imaging and spectroscopy approach cellular resolution, the proportionality of SNR to volume has dramatic effects. A reduction in voxel size from (1mm)3 to (10µm)3 results in a signal reduction of 106 [1] simply due to the reduction in the number of spins in the voxel generating the signal. This significant reduction in SNR when dealing with mass-limited and volume-limited samples is usually compensated by using strong static magnetic fields, superconducting receiver coils [2] or small, highly sensitive RF receiver coils [3]. As shown in [1,3], the MR signal reception sensitivity is dramatically enhanced when using micro-coils to closely conform to small samples. Therefore, an intense research effort has been focused towards manufacturing of coils with submillimeter dimensions for cell level MRI. Peck et al. [1] report on a hand-winding technique to manufacture solenoidal microcoils with diameters down to 50µm around hollow glass capillary tubes used as sample holders. Another complicated process [4] employs micro-contact printing followed by electroplating of a micro-coil around a capillary. Dohi et al. [5] report on a MEMS-compatible technique combining surface micromachining and a post-release folding process followed by electroplating. Most of the previously reported attempts to manufacture MRI micro-coils are either delicate techniques or serial processes incompatible with batch-fabrication, with direct implications on reproducibility and yield. Our group has recently demonstrated [6] a robust, fast and fully MEMS-compatible process for on-wafer integration of 3D micro-coils by exploiting the unique capabilities of an automatic wirebonder in conjunction with microfabrication techniques. In this paper, we report for the first time on the applicability of 3D solenoidal micro-coils in magnetic resoThirteenth International Conference on Miniaturized Systems for Chemistry and Life Sciences November 1 - 5, 2009, Jeju, Korea Thirteenth International Conference on Miniaturized Systems for Chemistry and Life Sciences November 1 - 5, 2009, Jeju, Korea

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nance imaging at microscale, as well as on a design concept to integrate the 3D micro-coils and microfludic channels in a Bio-MEMS platform for high-throuput cell level MRI. DEVICE FABRICATION The fabrication process of the 3D micro-coils is described in detail in [6]. CrAu (50/500nm) is sputtered on a Pyrex wafer and UV-patterned to define the metal pads needed to wind the micro-coils. A 500µm thick SU8 2150 layer is casted and patterned by UV photolithography to define hollow cylinders which act both as support for micro-coils and as sample holders. Micro-coils are wound around the SU8 sample holders using an automatic wirebonder [6] – Figure 1. Although microcoil winding is a serial process, it is fast (approx. 200ms per coil), reproducible and compatible with standard MEMS fabrication techniques.

Figure 1: a) SEM picture of a representative micro-coil wound around an SU8 micro-vial; b) Micro-coil resistance and inductance versus frequency; Q=45@400MHz; c) S11 reflection coefficient of the tuned and matched micro-coil. EXPERIMENTAL In order to asses the viability of our 3D solenoidal micro-coils for MRI, we have tested a micro-coil with the following characteristics: 5 windings using insulated Au wire with a diameter of 25!m. The inductance of the micro-coil is 40nH and the resistance measured at 400MHz (water Larmor frequency at 9.4T) is 2.25" yielding a Q of 45 and a reflection coefficient for the tuned and matched coil S11 of -25dB. The SU8 sample holder with an inner diameter of 700!m was filled with CuSO4doped water and the micro-coil was operated in transceive mode. MR images with 10x10!m2 (Figure 2abc) in-plane resolution were obtained using a standard FLASH sequence with the following parameters: TR/TE (repetition time/echo time) = 300/6.4 ms, flip angle 30 degrees, 6 averages, 5min scan time. The measured SNR is 47. The SU8 sample holder diameter (700!m) and height (450!m) are clearly depicted in Figure 2, leading to a sensitive volume of 0.17!l. This sensitive volume corresponds to the entire volume of the SU8 micro-vial surrounded by windings. We also report on the integration of the micro-coils with microfluidic channels and control valves in a Bio-MEMS platform for parallel, high-throughput MR investigation. The 2D array of micro-coils and SU8 sample holders is planarized by embedding in a PDMS scaffold. Separately, a 2-layer PDMS structure with microfluidic channels and control valves is fabricated as shown in [7]. The planarized micro-coil array and the 2-layer PDMS structure are bonded using O2-plasma. A schematic of the Bio-MEMS platform is shown in Figure 3a. Figure 3b presents a PDMSplanarized 2D array of micro-coils. Figure 3c demonstrates microfluidic functionality of the platform: ink is flushed through the channel and then the micro-coil is sealed using the control PDMS layer.

Thirteenth International Conference on Miniaturized Systems for Chemistry and Life Sciences November 1 - 5, 2009, Jeju, Korea

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Figure 2: MR images of water sample doped with CuSO4 enclosed in the SU8 microvial: a) the slice is oriented perpendicular to the micro-coil axis; b) the slice is oriented parallel to the micro-coil axis; c) 3D reconstruction of the microcoil sensitive volume.

Figure 3: a) Schematic of the Bio-MEMS platform; b) Array of planarized microcoils – SEM image; c) Planarized micro-coil with microfluidic channel and control valve on top. CONCLUSIONS We have successfully tested the viability of our 3D micro-coils for microscale MRI. This work is one step forward on-chip integration of a high-throughput celllevel MRI device. ACKNOWLEDGEMENTS The authors acknowledge the funding by the EC through the NEST Project 028533. REFERENCES [1] T.L. Peck, R.L. Magin, and P.C. Lauterbur, Design and Analysis of Microcoils for NMR Microscopy, J. Magn. Resonance, vol. 108, pp. 114-124, (1995). [2] R.D. Black et al, A high-temperature superconducting receiver for nuclear magnetic resonance microscopy, Science, 259, pp. 793-795, (1993). [3] E. W. McFarland, A. Mortara, Three-dimensional NMR microscopy: Improving SNR with temperature and microcoils, Magn. Reson. Imag., 10, pp. 279-288, (1992). [4] J.A. Rogers et al., Using microcontact printing to fabricate microcoils on capillaries for high resolution proton nuclear magnetic resonance on nanoliter volumes, Appl. Phys. Lett., 70, pp. 2464-2466, (1997). [5] T. Dohi, K. Kuwana, K. Matsumoto, and I. Shimoyama, A standing micro coil for a high resolution MRI, Proc. of Transducers 2007, pp. 1313-1315, (2007). [6] V. Badilita et al., 3D High-Aspect Ratio, MEMS Integrated Micro-Solenoids and Helmholtz Micro-Coils, Proc. of Transducers 2009, pp. 1106-1109. [7] M.A. Unger et al., Monolithic Microfabricated Valves and Pumps by Multilayer Soft Lithography, Science, 288, pp. 113-116 (2000). CONTACT: Dr. Vlad Badilita: Phone: +49-761-203-7435; email: [email protected] * These authors have contributed equally to this work.

Thirteenth International Conference on Miniaturized Systems for Chemistry and Life Sciences November 1 - 5, 2009, Jeju, Korea

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