Final Report Summary - BIOPROBE (Organic bio-electronic neural probe for in vivo molecular sensing and stimulation) BiOprobe was aimed at developing an advanced biomedical tool that combines physiological sensing with externally controlled chemical stimulation for applications in neuroscience. Recording of neurological activity progressed through measurements of sensing electrodes or Organic electrochemical transistors (OECTs). Stimulation is accomplished through incorporation of organic electronic ion pumps (OEIPs). The development of such multifunctional probes required a combination of expertise in electronic materials and micro-fabrication, electronic instrumentation, and organic electronics. This project was focused on the design and fabrication of the actual probes, optimization and investigation of the individual recording sites and ion release elements, which will allow for in vivo monitoring of neuronal activity (carried out by collaborators) and simultaneous stimulation. Through collaborations with the microelectronics industry and partners in life sciences, the applications of OECT/OEIP probes in biomedical implants and sensors was exploited. During this project, the fellow trained on the fabrication and physics of organic electronic devices and on experiments for in vitro recording. The fellow met with the group of Prof. Magnus Berggren from Linkoping University in Sweden, and learned about fabrication and operation details of Organic Electronic Ion Pumps, and organized mutual exchanges of knowledge between the labs. He also interacted heavily with the lab of Dr. Christophe Bernards at the University of Aix-Marseille with which experiments are ongoing to validate in vitro and in vivo devices rat models and brain slices. The fellow designed and prepared a proof-of-principle prototype made of both an ion pump, and an array of sensing electrodes. The prototype was fabricated in a manner similar to that previously reported by the host group. Furthermore, the fellow developed/designed an approach to enhance the operation of OECTs for biological recordings. By tuning the device dimensions, the device can be made to operate with its maximum transconducance at zero applied gate bias. Such operation allows for a more simplified probe design as less precious real-estate is used for the recording element, and can be used for the ion-release component (OEIP), or other multi-modal component.Finally, the fellow tested the durability and robustness of the targeted fabrication scheme for final probe design. The recording and release elements, in the final form are fabricated on a 2 um thick parylene support. One concern regarding this fabrication is the sensitivity and durability of the individual multi-modal elements during handling and repetitive use. To this end, the fellow fabricated sensing elements on the parylene support, and tested the figures of merit of the elements after fabrication, after detachment from the glass slide used for fabrication, and after aggressive crumpling. The fellow found the device performance maintained over 90% of its original level after such aggressive handling.With these individual components in place, the fellow participated in various efforts to validate the devices both in vitro and in vivo. This included the fabrication, sterilization and culturing of rat hippocampal neurons on devices, recording of rat hippocampal slices, and in vivo testing of OECT based probes on epileptic rat models.
