(60g) Monitoring Magnetic Nanoparticle Synthesis Progress Using a Benchtop Magnetic Particle Relaxometer

Current tracer imaging techniques like positron emission tomography (PET) and singe photon emission computed tomography (SPECT) are valuable in imaging molecular level features but they utilize radioactive tracers. Magnetic Particle Imaging (MPI)¹, which makes use of biocompatible and non-radioactive iron oxide nanoparticles as tracers has been shown to have comparable resolution and applications in real-time cardiovascular² and cancer imaging³, cell labeling and tracking⁴, and magnetic fluid hyperthermia⁵. In MPI the image is obtained by localizing the signal induced by the magnetic particles using a magnetic field gradient with a field free point (FFP). The resolution of the image is influenced by the particle’s response to time varying magnetic fields, which can be assessed using a Magnetic Particle Relaxometer (MPR)⁶ or Magnetic Particle Spectrometer (MPS),⁷ which lacks the spatial imaging capability of an MPI scanner. This equipment provides a quick performance assessment of newly synthesized tracers. It can also be employed to explore interesting phenomena like tracking of particle growth during synthesis, evaluating particle aggregation, measuring changes in viscosity, studying particle interactions with tissue, and biomarker detection for disease diagnosis.

In this work we make use of MPR/MPS to study particle response by observing changes in the acquired signal strength and its full-width-at-half-maximum (FWHM), which is related to the achievable resolution in MPI. These can be affected by change in size of particles in an Extended LaMer semi-batch thermal decomposition synthesis⁸ that allows controlled growth of particles over time or changes in the environment surrounding the particles. In our preliminary work we were able to observe a drop in the FWHM, thus indicating an increase in expected MPI resolution, as the particle size increased with time during synthesis, without the need of time-consuming operation step as required in other characterization tools like SQUID magnetometry and transmission electron microscopy (TEM).

The custom-built MPR is inexpensive, sensitive, and small in size, thus showing a promise of being widely adopted in laboratory and commercial settings. Also, with the tests requiring less than a minute and a tiny amount of sample, we envision the MPR to serve as an efficient benchtop particle analyzer and a complementary characterization tool.

¹ B. Gleich and J. Weizenecker, Nature 435, 1214 (2005).

² J. Weizenecker, B. Gleich, J. Rahmer, H. Dahnke, and J. Borgert, Physics in Medicine and Biology 54, L1 (2009).

³ E. Y. Yu, M. Bishop, B. Zheng, R. M. Ferguson, A. P. Khandhar, S. J. Kemp, K. M. Krishnan, P. W. Goodwill, and S. M. Conolly, Nano Letters 17, 1648 (2017).

⁴ B. Zheng, M. P. von See, E. Yu, B. Gunel, K. Lu, T. Vazin, D. V. Schaffer, P. W. Goodwill, and S. M. Conolly, Theranostics 6, 291 (2016).

⁵ D. W. Hensley, Z. W. Tay, R. Dhavalikar, B. Zheng, P. Goodwill, C. Rinaldi, and S. Conolly, Physics in Medicine and Biology 62, 3483 (2017).

⁶ P. W. Goodwill, E. U. Saritas, L. R. Croft, T. N. Kim, K. M. Krishnan, D. V. Schaffer, and S. M. Conolly, Advanced Materials 24, 3870 (2012).

⁷ N. Garraud, R. Dhavalikar, L. Maldonado-Camargo, D. P. Arnold, and C. Rinaldi, AIP Advances 7 (2017).

⁸ M. Unni, A. M. Uhl, S. Savliwala, B. H. Savitzky, R. Dhavalikar, N. Garraud, D. P. Arnold, L. F. Kourkoutis, J. S. Andrew, and C. Rinaldi, ACS Nano (2017).