Implantable wireless optoelectronic devices for cancer surgical guidance and treatment

The limited depth penetration of light in tissue, caused by absorption and multiple scattering, is a major challenge for its use in diagnostics and treatment in vivo. To overcome this limitation, we have created a new platform of wirelessly powered implantable devices that can be injected into the body using a standard biopsy needle. In this dissertation, we developed versions of the device that can be used to improve the localization of non-palpable breast cancers during lumpectomy surgeries and to perform photoactivated therapy in deep tissue. The devices are equipped with wirelessly powered light-emitting diodes (LEDs), encapsulated in a biocompatible epoxy, and include an impedance-matching circuit and a miniature receiver coil optimized for wireless operation in the 6.78 MHz industrial, scientific, and medical (ISM) radiofrequency (RF) band. For surgical applications, the device is multi-colored to take advantage of the wavelength-dependence of light attenuation and provide the surgeon with precise visual position and distance guidance based upon changes in perceived color. Specifically, due to the significant differences in tissue optical absorption, the implant contains a red LED that is visible through thick tissue (several cm), while a blue LED is mainly visible superficially (<1 cm). The 1.5 x 9 x 2 mm prototype cylindrical device (volume of 27 mm3) currently fits into a 12-gauge needle, although additional miniaturization is possible. For demonstrating phototherapy, an implantable wireless device was designed to emit light with a wavelength of 573 nm to excite the green-absorbing dye Rose Bengal, which is an efficient type II photosensitizer. The combination of a wireless device as a light source and Rose Bengal as a photosensitizer was found to induce cell death in cultured HT-29 human colorectal adenocarcinoma cells. Time-dependent generation of protruding bubbles was observed in the photoactivated cells, suggesting cell death by light-induced pyroptosis and supporting evidence was gained by cell staining with the fluorescence probes Annexin-V FITC and Propidium Iodide. We believe that this new platform opens new opportunities in the field of photomedicine, particularly in the areas of surgical guidance and phototherapy for cancer treatment.