Papers

AVS2004 Session MI-TuA: BioMagnetism

Tuesday, November 16, 2004 1:20 PM in Room 304A

Tuesday Afternoon

Start	Invited?	Item
1:20 PM		MI-TuA-1 Synthesis and Surface Modification of Monodisperse Magnetic Nanoparticles for Biological Applications S. Sun, H. Zeng, H. Yu, D. Robinson (IBM T.J. Watson Research Center); G. Li, S. Wang, R. White (Stanford University) We present our chemical synthesis and surface modification of monodisperse magnetic nanoparticles for potential applications in bio-recognition. Biocompatible dispersions of magnetic nanoparticles have been used widely in bimolecular labeling and biological imaging, sensing and separation in recent years. These applications require that the particles be superparamagnetic at room temperature, and monodisperse for uniform biodistribution, bioelimination and contrast effects. The Co and Fe based magnetic nanoparticles, including metallic Co, Fe, CoFe and oxide MFe2O4 nanoparticles, have high magnetic moment, and thus sufficient sensitivity for magnetic detection. With proper functionalization, they can be useful candidates as magnetic probes for biomolecule identification. We have developed various synthetic procedures for making monodisperse magnetic nanoparticles. Using a combination of surfactants, such as oleic acid/oleyl amine, to control nanoparticle growth and stabilization, we can tune the size of the nanoparticles to obtain an optimum magnetic signal for sensor detection. By controlling particle surface chemistry and synthetic conditions, we can also produce multi-functional nanoparticles with either core/shell-structured particles, such as Fe3O4/AgSe or Fe3O4/FePt, or dumbbell-structured particles, such as Fe3O4-Ag. We can further transform the oleic acid/oleylamine capped, hydrophobic nanoparticles into hydrophilic ones by using tetramethylammonium hydroxide, bi-functional thiol molecules, or multi-functional polymeric molecules. These hydrophilic nanoparticles are both chemically and magnetically stable in phosphate buffer solution at neutral pH, and can withstand DNA denaturing and hybridization conditions. They are suitable as magnetic probes for highly sensitive bio-detection. Acknowledgement: The work is supported in part by DARPA under grant No. N00014-01-1-0885.
2:00 PM		MI-TuA-3 Progress in Non-Invasive Biomagnetic Liver Iron Store Measurements D.N. Paulson (Tristan Technologies) Biomagnetic liver susceptometry is a non-invasive measurement of liver (and spleen) iron stores. Proposed by Bauman in 1967, it was demonstrated on animals¹ shortly thereafter. With the development of the Superconducting quantum interference device (SQUID) magnetic field sensor, a prototype system was developed for measurement of human liver iron stores. Measurements on normal and iron overloaded subjects showed this technique to be an accurate quantitative measurement of human iron stores². The basic system is comprised of a superconducting magnet, a highly sensitive SQUID magnetic field sensor, a water bag (placed between the sensor and patient) that simulates the natural magnetism of the body, a non-magnetic bed and data acquisition system. Since the installation of the first clinical systems at Cleveland and Hamburg, over 6,000 clinical measurements have been made on over 4,000 patients. We describe the measurement technique and present summaries of a number of clinical studies comparing biomagnetic liver susceptometry to needle biopsies. We describe the current status of both the original systems³ and improved systems now being produced and comment on future directions in the non-invasive measurement of liver-iron stores including the possibility of assessment of cardiac iron. ¹ Bauman JH, Harris JW, "Estimation of hepatic iron stores by in-vivo measurement of magnetic susceptibility", J Lab Clin Med 1967; 70: 246-257. ² Brittenham GM, Farrell DE, Harris JW, Feldman ES, Danish EH, Muir WA, Tripp JH, Bellon EM."Magnetic-susceptibility measurement of human iron stores", N Engl J Med 1982; 307: 1671-1675. ³ Paulson DN, Fagaly RL, Toussaint RM, Fischer R, "Biomagnetic Susceptometer with SQUID Instrumentation", IEEE Transactions on Magnetics, vol 27, no. 2, March 1991.
2:40 PM		MI-TuA-5 Design Considerations for High Sensitivity Biosensing with Magnetic Labeling and Detection J.C. Rife (Naval Research Laboratory) We are developing the BARC (Bead ARray Counter) sensor chip for the detection of biomolecules labeled with magnetic microbeads.¹ Presently, 2.8 µm-diameter commercial magnetic beads are detected by an array of 64 GMR sensors on the chip, with each sensor spanning a 200 µm diameter spot. Arrays of single-stranded DNA or antibody probes are immobilized onto the sensor spots, and biomolecular targets (e.g. DNA or proteins) that are captured by the probes are then labeled with magnetic microbeads. Although at the limits of detection each bead labels a single captured molecule, non-specifically bound beads and sensor noise currently set the limit of detection to about 10 beads (potentially 10 molecules) per sensor. Although the sensor signal to noise can be improved, ultimately the sensitivity will be limited by delivery of molecules to the sensor surface as governed by diffusion, sensor geometry, and fluidics. The current BARC sensor array has an advantage because of its relatively large sensors, and can presently detect DNA concentrations as low as 1 fM (10⁵ molecules/cm³). Further improvement in the sensitivity will require coupling the design of the fluidics with the sensor array. I will discuss the BARC sensor response, along with finite element calculations of the delivery of molecules to the surface under various conditions. I will also discuss how these issues affect various alternative magnetic labeling and detection approaches, such as those based on spin valves and SQUIDs. This work done in collaboration with M. M. Miller, P. E. Sheehan, C. R. Tamanaha, M. Tondra, and L. J. Whitman. ¹J. C. Rife et al., Sensors and Actuators A 107, 209-218 (2003).
3:20 PM		MI-TuA-7 Advances in MR Elastic Displacement Imaging and Non-invasive Measurements of Myocardial Compliance H. Wen (NHLBI/NIH) The vector nature of the NMR signal gives rise to a group of displacement imaging methods in magnetic resonance imaging that are based on spin phase-shifts. They are suited for studying physiological motions such as the heartbeat and elastic reponses of arterial walls to the blood pressure. Elevated myocardial stiffness is a cause of high diastolic blood pressure and congestive heart failure. The traditional measure of heart chamber stiffness uses diagnostic catheterization, an invasive procedure not acceptable for many patients. MR elastic displacement imaging is a new way to estimate material viscoelastic parameters non-invasively. It has been validated in animal models and shown feasible in humans. Clinical trials to detect heart and artery stiffening in patients with congenital heart disease are being prepared.