Periodic Reporting for period 2 - OPTEL-MED (Optoelectronic medicine - nerve cell regulation with light)
Reporting period: 2022-07-01 to 2023-12-31
The project is driven by answering milestone scientific questions in device physics, photoelectrochemistry, and electrophysiology, however the project is simultaneously designed to tackle an important clinical application: vagus nerve stimulation (VNS). We will apply our findings to implement an implantable stimulator actuated transcutaneously by portable light sources. We will develop standard operating procedures for chronic optoelectronic VNS in rodent animal models, paving the way for future clinical trials. The application to VNS is motivated by the fact that at present the vagus nerve is the peripheral nerve with that largest number of patients receiving bioelectronic therapy. It is important to note that the science and technology developed in OPTEL-MED is not limited to the vagus nerve only, and can be deployed to other peripheral nerve targets. Success with vagus nerve models is expected to stimulate cross-over into other applications.
We had to develop different varieties of photocapacitors for VNS in mice. The first tests were challenging and not successful, and smaller different nerve interfaces had to be developed. In the end, we have been successful in acute VNS, and our findings are under review. We are now moving towards chronic experiments.
Aside from peripheral nerves, we proposed to explore photocapacitors for stimulation of the brain. We utilized photocapacitors as wireless cortical stimulation electrodes, and demonstrated that they can be actuated through the skull: J. Neural Eng. 18, 066016 (2021).
In paralel, we have made progress with the concepts for charge delivery which were anticipated in the proposal. One route is structuring of photocapacitors into micropyramid architectures: Nanotechnology 33, 245302 (2022). We continue with other routes of charge concentration by connecting charge generation elements to microelectrodes, which provide more spatial control of stimulation. A related aim is to create structures surfaces which can be better interfaced and immobilized to tissue. To this end, we have demonstrated the use of 3D foldable conductors: Adv. Electron. Mater. 2001236, (2021).
One of the primary aims of the project was more fundamental exploration of photoelectrical stimulation, mechanistically at the level of cell interfaces. We have made significant progress in two of the planned areas: studying reactive oxygen species formation at electrodes; and understanding of the mechanisms of capacitive coupling which govern the efficiency of stimulation.
In the topic of oxygen electrochemistry, we have conducted a detailed survey of many electrode materials and established a novel method of directly probing oxygen and hydrogen peroxide concentrations. We found, to our surprise, that established neurostimulation protocols produce very significant changes in local oxygen chemistry. We hypothesized that some conditions cause irreversible oxygen chemistry, but our findings exceeded our hypothesis: J. Neural Eng. 19, 036045 (2022). and have received a lot of feedback from the bioelectronics community due to this publication. As the findings are both surprising and generally applicable to all neurostimulation protocols (not just the photoelectrical work we concentrate on in OPTEL-MED).
Another important aspect of oxygen electrochemistry we studied at the level of peroxide-sensitive ion channels. We developed a unique tool for delivering "on demand" peroxide which was used to modify the behavior of potassium ion channels, which has important (electro)physiological consequences Adv. Sci. 9, 2103132 (2022). This work also surpassed our expectations in terms of results and response from the community, and we are actively pursuing this research direction.
We recently published a detailed study of understanding photocapacitive coupling with cells: doi:10.1002/admt.202101159. This is a fundamental and important milestone which guides development of photocapacitor technology.