Wireless implants for increased signal sensitivity of nuclear magnetic resonance monitoring of a bio-artificial pancreas

摘要

The non-invasive monitoring of bio-engineered organs using nuclear magnetic resonance (NMR) imaging and spectroscopy is crucial in the development of a bio-artificial pancreas capable of providing physiological blood glucose regulation for the treatment of type 1 diabetes. Current monitoring techniques are limited in providing sufficient NMR signal sensitivity at multiple frequencies, which hinders the ability to fully characterize the tissue-construct functionality post-implantation. This work investigates the design of implantable electronics capable of increasing NMR signal sensitivity over a 190MHz - 470MHz frequency range through complete wireless control to enable detailed visualization and characterization of an implanted bio-artificial pancreas. A highly-integrated implantable device is developed to selectively resonate a NMR detection coil across a frequency range spanning important metabolic nuclei including 1Hydrogen, 19Flourine, and 31Phosphourus. Device functionality was validated through 1H NMR images acquired within tissue-equivalent gel phantom and small animal studies, which increased the acquired signal sensitivity by 140% (7.7dB) and 80% (5.3dB) within 4.7T (ƒ = 200MHz) and 11.1T (ƒ = 470MHz) magnetic-fields respectively and provided signal enhancement of high-resolution images up to 73% (4.8dB). Untethered operation of the implant is enabled through a staggered resonant-based wireless transmission scheme that provides uniform energy transfer across a range of possible implant locations while increasing the maximum transmission distance up to a factor of two. Analytical models and experimental measurements of the energy transfer characteristics of the wireless topology are compared with a typical near-field inductive link. A wireless implantable NMR acquisition coil is also proposed to increase NMR signal sensitivity through the amplification and transmission of the NMR response to an external base-station. A test-chip is designed and experimentally validated as part of the implantable system for the amplification and demodulation of pA to nA differential currents with 179.9dB (1nA/V) current-to-voltage gain, 16.2kHz bandwidth, and 177.5fA/Hz ½ input referred current noise.