Localization of microscale devices in vivo using addressable transmitters operated as magnetic spins

Nat Biomed Eng. 2017 Sep;1(9):736-744. doi: 10.1038/s41551-017-0129-2. Epub 2017 Sep 12.

Abstract

The function of miniature wireless medical devices, such as capsule endoscopes, biosensors and drug-delivery systems, depends critically on their location inside the body. However, existing electromagnetic, acoustic and imaging-based methods for localizing and communicating with such devices suffer from limitations arising from physical tissue properties or from the performance of the imaging modality. Here, we embody the principles of nuclear magnetic resonance in a silicon integrated-circuit approach for microscale device localization. Analogous to the behaviour of nuclear spins, the engineered miniaturized radio frequency transmitters encode their location in space by shifting their output frequency in proportion to the local magnetic field; applied field gradients thus allow each device to be located precisely from its signal's frequency. The devices are integrated in circuits smaller than 0.7 mm3 and manufactured through a standard complementary-metal-oxide-semiconductor process, and are capable of sub-millimetre localization in vitro and in vivo. The technology is inherently robust to tissue properties, scalable to multiple devices, and suitable for the development of microscale devices to monitor and treat disease.