The progress of biomedical devices over the past decades is changing how we think about diagnostics and therapeutics. Nowadays, small medical devices can diagnose and treat disease from inside the body targeting neurological and autoimmune disorders, cardiovascular conditions, cancer, and other diseases. For instance, smart pills are being used to image the gastrointestinal tract, distributed sensors are being developed to map the function of the brain, and microscale robots are being designed to access organs through the blood stream. However, a major challenge remains in the way these devices communicate with the outside world. Existing electromagnetic, acoustic, and imaging-based methods for localizing and communicating with such devices with spatial selectivity are limited by the physical properties of tissue or the performance of the imaging modality. Similarly, most of the current methods for monitoring biophysical electromagnetic signals in opaque tissue suffer from poor spatial resolution or other technology-dependent limitations (e.g., tethered devices, poor sensitivity, highly invasive). Here, we propose to address both challenges by developing an alternative approach for the minimally invasive monitoring and control of biophysical processes with high-precision and high-resolution using microscale biomimetic devices. Specifically, we will adapt the behavior of nuclear spins in magnetic resonance imaging (MRI) to engineer MRI-controllable resonant-circuit-based microsystems whose resonance frequency and tuning depend on the local magnetic field and bio-electromagnetic signal, respectively. The application of magnetic field gradients and radio-frequency signals (available in MRI) then allows the imaging of localized biophysical processes. These Wireless Electronic MRI Agents (WEMA) will be developed using integrated circuit (IC) technology and will be compatible with MRI-instrumentation. We will use a small animal 7 T MRI instrument (available at USC) as our initial system. As a proof-of-concept, we will target the detection of Chron?s disease using photoluminescence-enabled WEMA devices, addressing the need for accurate and early diagnosis in inflammatory small bowel disorders. If successful, this transformative technology will provide a new biomimetic platform capable of wireless, distributed, minimally-invasive sensing and control of biophysical processes using MRI, and will enhance the development of a wide range of biomedical applications, from distributed monitoring of relevant biomarkers to targeted release of therapeutic agents and tissue imaging for disease diagnosis. We will achieve the proposed overall goals by pursuing the following major aims:
Specific Aim 1 : Develop miniature WEMA devices via IC design.
Specific Aim 2 : Develop MRI methods to interface with WEMA devices.
Specific Aim 3 : Experimental validation of WEMA technology in vivo.
Besides the significant progress of biomedical devices for the diagnosis and treatment of disease from inside the body, a major challenge remains in the way these devices communicate with the outside world and in how biophysical processes are monitored deep inside the body in opaque tissue. Here, we propose to address both challenges by developing an alternative approach for the minimally invasive monitoring and control of biophysical processes with high-precision and high-resolution using microscale biomimetic devices and integrated circuit technology. We will adapt the behavior of nuclear spins in magnetic resonance imaging (MRI) to engineer MRI-controllable resonant-circuit-based microsystems to act as Wireless Electronic MRI Agents (WEMA), enabling electronic control of biophysical electromagnetic processes in opaque tissue for diagnostics and therapeutics.
