Conjugated polymer bio-hybrid interfaces for artificial retina and light-control of living cells

This thesis is concerned with the design, realization and opto-electronic characterization of a bio-hybrid interface, based on semiconducting polymers, presented as a new generation of Artificial Retina model and a novel platform for light-control and stimulation of living cells. Bioelectronics is a fast-growing field. It concerns the interface between electronics and biology. It has the potential to significantly affect healthcare and medicine by introducing scientific breakthroughs in medical therapies or prosthetic devices, improving lives of people with disabilities and diseases. Organic electronic materials are largely used in bioelectronics. In fact, these materials can overcome limitations of rigid standard electronic matter due to their unique features such as the “soft” nature, the ability to conduct ions, and biocompatibility. Nowadays there is a novel emerging field in this scenario: optobio electronics. Among organic electronic materials, there are light sensitive conjugated polymers. Semiconducting polymers used as photoactive layers claiming biocompatibility can offer excellent optoelectronic and mechanical properties such as visible light absorption, solution processability, the possibility of using flexible substrates, and easy tunability of color sensitivity. Thus, light sensitive conjugated polymers have been largely investigated as new interfaces for optical modulation of bioelectrical activity in several types of in vitro cell cultures, such as primary neurons and astrocytes, and in tissues, mostly explanted retinas from different animal models. This thesis presents a novel concept of bio-hybrid opto-electronic device. It is a new interface for in vitro light-control and stimulation of living cells and for investigating Artificial Retina models with the aim of sight restoration. The approach has been to investigate the double aspect of bioelectronics based on photosensitive biocompatible organic polymers i.e. the stimulation and the detection of biological signals both at the cellular and tissue level. The main objectives of this work are detailed in six chapters, as described below: Chapter 1: The basic concepts about biological systems are reviewed. Living cells and the plasma membrane, the retina and retinal diseases are briefly introduced. The main principles behind the bioelectricity and electrophysiology are discussed. To contextualize the work a state of art on electrical stimulation of retina and the visual prosthetic devices, based on inorganic electronics, which have had already a clinical trial is performed. Chapter 2: Organic Bioelectronics fundamentals are reviewed. The new opto-bio electronic field is introduced with special highlight on semiconducting polymers. An introduction on photovoltaic semiconducting polymers and a brief description of the occurring photovoltaic process are discussed. Then a state of the art analysis on semiconducting polymers interfaced with biological systems is discussed, with a focus on the artificial retinas studies using organic semiconductors. The concept of bio-hybrid device is introduced. Chapter 3: The experimental tools and techniques used for the design, fabrication and characterization of the conjugated polymer bio-hybrid device are reviewed. Chapter 4: The bio-hybrid photovoltaic device working principles and optoelectrical characterization are presented. The device optimization as a color-sensitive conjugated polymer ink-jet-printed pixelated artificial retina model is described. Finally, a water transfer method as a proof of concept for a possible artificial retina implantation is introduced. Thus, possible future application in tissue engineering and visual prosthesis are discussed. This work was in collaboration with Advanced Technology Institute, Department of Electrical and Electronic Engineering, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford, UK; Cicci Research s.r.l., Italy; Istituto di Struttura della Materia, CNR-ISM, Italy; European Molecular Biology Laboratory, Epigenetics and Neurobiology Unit, Italy; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy. A scientific manuscript has been submitted (as first author). Chapter 5: The conjugated polymer bio-hybrid interface is presented here as a photo-electrochemical cell for in vitro light control and stimulation of living cells. Biocompatibility is demonstrated by cytotoxic kit-experiment. Light stimulation of living xxxviii cells onto polymer substrates may lead to changing in membrane potential. Neuroblastoma cells (SH-SY5Y) are investigated. We also unravel the possibility to control cells proliferation under light-treatment, when seeded and grown onto the bio-hybrid device photoanodic electrode. A scientific manuscript in collaboration with Department of Biomedicine and Prevention, University of Rome Tor Vergata is being prepared (as first author). Chapter 6: Conclusion and future prospects are discussed.