Nanodiamond Imaging: a New Molecular Imaging Approach

Nanodiamond imaging is a novel biomedical imaging technique that non-invasively records the distribution of biologically-tagged nanodiamonds in vivo, in two or three dimensions. A nanodiamond imaging system optically detects electron spin resonance of nitrogen-vacancy centers in nanodiamonds, a non-toxic nanomaterial that is easily biologically functionalized. Two systems were built to demonstrate the feasibility of the technique. Using the first system, we imaged 2D projections of multiple nanodiamond targets within pieces of chicken breast; it is the first demonstration of imaging within scattering tissue by optically-detected magnetic resonance. The first system achieves a sensitivity equivalent to 740 pg of nanodiamond in 100 s of measurement time with a spatial resolution of 800 μm over a 1 cm2 field of view. The second system was built with a field of view large enough to image a mouse, and with the capability to acquire multiple 2D projections of the subject for 3D reconstruction of the nanodiamond distribution.In this thesis, we briefly review existing imaging modalities. We show how nanodiamond imaging has the potential to image with both high sensitivity AND high spatial resolution over organism-scale fields of view, features which are mutually exclusive in existing modalities (except at the shallowest imaging depths). Nanodiamond imaging's combination of high sensitivity and high resolution is potentially one of its greatest advantages. With reasonable sensitivity increases we expect to achieve a sensitivity of 100 fg and potentially as low as 25 ag; spatial resolution could reasonably be extended to <100 μm and is only limited by the strength of the magnetic gradient. We discuss practical ways to achieve these sensitivity increases, including various different modulation schemes.We also review the nitrogen-vacancy center and its optically-induced spin polarization and optical spin detection mechanisms starting from a group-theoretic understanding of its energy levels. We build upon knowledge of the nitrogen-vacancy center, starting from its spin Hamiltonian, to present a model of the optically-detected magnetic resonance lineshape of nitrogen-vacancy centers in nanodiamond powder. This model is compared to measurements. We explore the imaging point-spread function and show how imaging at just above the NV zero-field frequency--2.872 GHz, rather than 2.869 GHz--improves the contrast.Details of the imaging systems are discussed, including the stable source of optical excitation provided by band-pass-filtered LEDs, and the sensitive optical detection provided by custom-built photodiode amplifiers that were shielded to reject microwave interference. Other detailed subsystems designed and constructed for these imaging systems include electromagnet coils and multichannel bipolar magnet power supplies, and software for experiment control and signal processing