1H NMR Detection of superparamagnetic nanoparticles at 1T using a microcoil and novel tuning circuit.

Magnetic beads containing superparamagnetic iron oxide nanoparticles (SPIONs) have been shown to measurably change the nuclear magnetic resonance (NMR) relaxation properties of nearby protons in aqueous solution at distances up to approximately 50 microm. Therefore, the NMR sensitivity for the in vitro detection of single cells or biomolecules labeled with magnetic beads will be maximized with microcoils of this dimension. We have constructed a prototype 550 microm diameter solenoidal microcoil using focused gallium ion milling of a gold/chromium layer. The NMR coil was brought to resonance by means of a novel auxiliary tuning circuit, and used to detect water with a spectral resolution of 2.5 Hz in a 1.04 T (44.2MHz) permanent magnet. The single-scan SNR for water was 137, for a 200 micros pi/2 pulse produced with an RF power of 0.25 mW. The nutation performance of the microcoil was sufficiently good so that the effects of magnetic beads on the relaxation characteristics of the surrounding water could be accurately measured. A solution of magnetic beads (Dynabeads MyOne Streptavidin) in deionized water at a concentration of 1000 beads per nL lowered the T(1) from 1.0 to 0.64 s and the T2 * from 110 to 0.91 ms. Lower concentrations (100 and 10 beads/nL) also resulted in measurable reductions in T2 *, suggesting that low-field, microcoil NMR detection using permanent magnets can serve as a high-sensitivity, miniaturizable detection mechanism for very low concentrations of magnetic beads in biological fluids.

[1]  G. Whitesides,et al.  Using microcontact printing to fabricate microcoils on capillaries for high resolution proton nuclear magnetic resonance on nanoliter volumes , 1997 .

[2]  Richard L. Magin,et al.  Miniature permanent magnet for table‐top NMR , 2003 .

[3]  C. Slichter Principles of magnetic resonance , 1963 .

[4]  P. Freitas,et al.  High sensitivity detection of molecular recognition using magnetically labelled biomolecules and magnetoresistive sensors. , 2003, Biosensors & bioelectronics.

[5]  Alan P Koretsky,et al.  MRI detection of single particles for cellular imaging. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Eiichi Fukushima,et al.  Experimental pulse NMR : a nuts and bolts approach , 2018 .

[7]  M. V. Shutov,et al.  Development of low field nuclear magnetic resonance microcoils , 2005 .

[8]  P.-A. Besse,et al.  High-Q factor RF planar microcoils for micro-scale NMR spectroscopy , 2002 .

[9]  J. Sweedler,et al.  Capillary isotachophoresis/NMR: extension to trace impurity analysis and improved instrumental coupling. , 2002, Analytical Chemistry.

[10]  André Briguet,et al.  Micro-spectrometer for NMR: analysis of small quantities in vitro , 2004 .

[11]  Charles Pennington,et al.  Triaxial magnetic field gradient system for microcoil magnetic resonance imaging , 2000 .

[12]  Radivoje Popovic,et al.  Superparamagnetic microbead inductive detector , 2005 .

[13]  Kevin R. Minard,et al.  Solenoidal microcoil design—part II: optimizing winding parameters for maximum signal-to-noise performance , 2001 .

[14]  Scott D. Collins,et al.  A Micromachined Double-Tuned NMR Microprobe , 2003 .

[15]  Richard L. Magin,et al.  NMR spiral surface microcoils: Design, fabrication, and imaging , 2003 .

[16]  R. Weissleder,et al.  A pilot study of lymphotrophic nanoparticle-enhanced magnetic resonance imaging technique in early stage testicular cancer: a new method for noninvasive lymph node evaluation. , 2005, Urology.

[17]  A. Pühler,et al.  Comparison of a prototype magnetoresistive biosensor to standard fluorescent DNA detection. , 2004, Biosensors & bioelectronics.

[18]  H. Carr,et al.  The Principles of Nuclear Magnetism , 1961 .

[19]  Jonathan V. Sweedler,et al.  High-Resolution NMR Spectroscopy of Sample Volumes from 1 nL to 10 μL , 1999 .

[20]  N. Bander,et al.  In vitro characterization of radiolabeled monoclonal antibodies specific for the extracellular domain of prostate-specific membrane antigen. , 2000, Cancer research.

[21]  T. Matsunaga,et al.  Novel detection system for biomolecules using nano-sized bacterial magnetic particles and magnetic force microscopy. , 2005, Journal of biotechnology.

[22]  Richard L. Magin,et al.  Integrating microfabricated fluidic systems and NMR spectroscopy , 2000, IEEE Transactions on Biomedical Engineering.

[23]  N F de Rooij,et al.  Planar microcoil-based microfluidic NMR probes. , 2003, Journal of magnetic resonance.

[24]  A. Webb,et al.  Signal-to-noise and magnetic susceptibility trade-offs in solenoidal microcoils for NMR. , 1996, Journal of magnetic resonance. Series B.

[25]  E. Radue,et al.  Characteristics of ultrasmall superparamagnetic iron oxides in patients with brain tumors. , 2005, AJR. American journal of roentgenology.

[26]  R. McDermott,et al.  Ultrasensitive magnetic biosensor for homogeneous immunoassay. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[27]  A. Forchel,et al.  Fabrication of NMR - Microsensors for nanoliter sample volumes , 2000 .

[28]  Daniel L Graham,et al.  Magnetoresistive-based biosensors and biochips. , 2004, Trends in biotechnology.

[29]  Kevin R. Minard,et al.  Solonoidal microcoil design: optimizing RF homogeneity and coil dimensions , 2001 .

[30]  Dmitri Artemov,et al.  MR molecular imaging of the Her‐2/neu receptor in breast cancer cells using targeted iron oxide nanoparticles , 2003, Magnetic resonance in medicine.

[31]  H. Wensink,et al.  High signal to noise ratio in low field NMR on chip, simulations and experimental results , 2004, 17th IEEE International Conference on Micro Electro Mechanical Systems. Maastricht MEMS 2004 Technical Digest.

[32]  Vincent Malba,et al.  Laser-Lathe Lithography—a Novel Method for Manufacturing Nuclear Magnetic Resonance Microcoils , 2003 .

[33]  Michael J. Vasile,et al.  MICROFABRICATION BY ION MILLING : THE LATHE TECHNIQUE , 1994 .

[34]  Nicole Pamme,et al.  Magnetism and microfluidics. , 2006, Lab on a chip.

[35]  M. D. Alper,et al.  Detection of bacteria in suspension by using a superconducting quantum interference device , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[36]  P C Lauterbur,et al.  Design and analysis of microcoils for NMR microscopy. , 1995, Journal of magnetic resonance. Series B.