Localization of Microscale Devices In Vivo using Addressable Transmitters Operated as Magnetic Spins
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.
© 2017 Macmillan Publishers Limited, part of Springer Nature. Received: 24 April 2017; Accepted: 01 August 2017; Published online: 12 September 2017. The authors thank A. Agarwal for insightful discussions and assistance with the chip design, and A. Shapero for assistance with chip encapsulation. We thank K.-C. Chen, M. Raj, B. Abiri, A. Safaripur, F. Bohn, H. Davis, P. Ramesh and G. Lu for helpful and constructive discussions. We appreciate the help and assistance of the Caltech High-speed Integrated Circuits group. This research was supported by the Heritage Medical Research Institute (M.G.S. and A.E.), the Burroughs Wellcome Fund (M.G.S.) and the Caltech Rosen Bioengineering Center graduate scholarship (M.M.). Author Contributions: M.M., M.G.S. and A.E. conceived and planned the research. M.M. designed the integrated circuit and all printed circuit boards, and developed the code to program the FPGA. M.M. performed characterization and in vitro experiments. M.M. and A.L.-G. performed in vivo experiments. M.M. analysed data. M.M., M.G.S. and A.E. wrote the manuscript with input from all other authors. M.G.S. and A.E. supervised the research. The authors declare no competing financial interests.
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