Bioelectronic Medicine PDF Download

The use of electronic devices in medical care is one of the main targets of precision medicine. The field of bioelectronic medicine uses electronic devices to diagnose or treat diseases and disorders in a complementary or alternative way to chemical drugs. It has been more than sixty years since the world’s first implantable battery-driven cardiac pacemaker was implanted here in Sweden. Since then, electronic therapies have been implemented for neurological disorders such as Parkinson’s disease, epilepsy, sensory and motor function restoration, and many more. However, electronics can also be used for delivery of conventional drugs in a more controlled, localized, and specific fashion. Therapeutic utility and patient comfort are maximized when the devices are as minimally invasive as possible. The most important milestone in the development of the cardiac stimulator was making it wireless. The early versions of the device required bulky parts to be placed outside of the body with transcutaneous electrical leads to the target site which led to high infection risk and frequent failures. To date, batteries remain the most common way to power implantable electronics. However, their large size and the necessity for replacement surgeries makes the technology relatively invasive. Alternative approaches to wireless power transfer are thus sought after. The most promising technologies are based on electromagnetic, ultrasound, or light-coupling methods. The aim of this thesis is to utilize tissue-penetrating deep red light for powering implantable devices. The overarching concept is an organic photovoltaic based on small molecule donor-acceptor bilayer junctions, which allows for ultrathin, flexible, minimally-invasive devices. Within this thesis, the photovoltaic device was utilized in two ways. Firstly, the photovoltaics are fabricated to act as an integrated driver for other implantable electronic components: 1) an organic electronic ion pump for acetylcholine delivery; 2) a depth-probe microelectrode stimulation device for epilepsy applications. Secondly, an alternative device, the organic electrolytic photocapacitor, is formed by replacing one of the solid electrodes by an electrolytic contact, thus yielding a minimalistic device acting as a direct photoelectrical stimulator. Within the thesis, the photocapacitive stimulation mechanism is validated by studying voltage-gated ion channels in a frog oocyte model. Next, two lithography-based patterning techniques are developed for fabricating these devices with better resolution and on flexible substrates suitable for in vivo operation. Finally, a chronic implant is demonstrated for in vivo sciatic nerve stimulation in rodents. The end result of this thesis is a series of novel device concepts and methods for stimulation of the nervous system using deep red light.