Nuclear Magnetic Resonance Readable Sensors

The monitoring of physiological biomarkers is fundamental to the diagnosis and treatment of disease. We describe here the development of molecular sensors which can be read by magnetic resonance (MR) relaxometry. MR is an advantageous bio-sensor readout because it can be determined from opaque samples and through intervening layers of matter. Wash steps can therefore be avoided in in vitro MR assays and non-invasive interrogation achieved for in vivo MR sensing. Functionalized magnetic nanoparticles originally developed as in vivo contrast agents have recently been adapted for use in magnetic relaxometry assays. The first half of this thesis describes a simple particle functionalization strategy and its application to the detection of myocardial infarction ("heart attack") associated biomarkers. The particles were subcutaneously implanted in the form of small discrete sensors and shown to be efficacious in measuring the physiological release of three protein biomarkers. Alternative contrast mechanisms may also be employed by MR readable sensors. The second half of this thesis introduces the novel use of 'smart' polymers which produce analyte-responsive changes in MR relaxivity. We show that MR responsive calcium-crosslinked and pH-swelling hydrogels can be incorporated within discrete sensors. Thesis Supervisor: Michael J. Cima Title: Sumitomo Electric Industries Professor of Engineering