Organic electronics at the interface with bio-medicine

The work carried out in this PhD thesis falls into the domain of the Organic Bioelectronics. This field, outstandingly emerged in the last few years, combines several disciplines, mainly Organic Electronics, that relies on carbon-based semiconductors, and biomedicine, in its connotations related to biosensors and diagnostics. In particular, this work concerns the development and study applications of electrochemical devices based on organic conductors for bio-sensing and bioelectronics, applied in particular to the detection of molecules and biologicallyrelevant systems, cellular stress induced by drugs and control of bacterial adhesion. The relevant results obtained qualify electrochemical devices as very promising for biomedical applications in a perspective of cheap, easy to handle systems that could contribute to the development of point-of-care diagnostics and theranostics. Chapter 1 provides the basic theoretical background for the themes and questions that motivate this work. First, the basic concepts of Organic Electronics are illustrated in detail, providing a description of the physical properties that make organic semiconductors an extremely interesting class of materials. The applications of organic-based devices are described, focusing in particular on Organic Electrochemical Transistors (OECTs), a type of Organic Thin film Transistor (OTFT) that represents the device of choice in the present work. An overview on Organic Bioelectronics is also given, with a special focus on recent applications of OECTs to bio-sensing and cellular biology. Finally, a discussion of questions concerning sensing of bio-molecules and biologically-relevant systems (melanins and nano-particles, respectively) is given, together with an introduction to biofouling and cellular stress. Chapter 2 deals with the demonstration that OECTs can efficiently sense biologically relevant pigment molecules, such as eumelanin. Its electrical properties were also studied by exploring redox reactions that occur at the gate electrode providing appropriate experimental conditions. Of particular interest is that the study of the electrical measurements gives information on stability and evolution of these bio-molecules in response to electrochemical stress. Such changes shall be deemed to be the basis of the peculiar properties and the role of melanin within biological organisms. Chapter 3 discusses another field of application of OECTs, addressing the detection and monitoring of magnetic nanoparticles functionalized with polymeric shell, widely studied as drug delivery systems and for hyperthermia in cancer treatments. Monitoring of the electrical response of OECTs allowed to sense such nano-systems as a function of their concentration. Here it is demonstrated that OECTs represent a valuable tool for low-cost and real-time monitoring the dynamics of such systems in an aqueous solutions. Control of bacterial adhesion and biofilm formation by means of conducting polymers is the central topic of Chapter 4. The role of surface properties is studied on the ability of E. coli bacteria to adhere and form the systems known as biofilms. Devices based on two of the most used organic conductors, PEDOT:PSS and PEDOT:Tos, were designed and manufactured, with the aim of modulating the surface adhesion properties by simply electrically controlling the polarization of the conducting polymers. The outcome of this project shows that the redox state of the surface plays a key role in promoting (or inhibiting) the formation of bacterial biofilms. We hence obtained new information on the technologies and methods used to control biofilms, which are often detrimental impact but in some cases beneficial in processes with high social impact. In a contest of increasing complexity, Chapter 5 deals with interfacing of OECTs with biological systems, such as mammalian cells, to develop a system for sensing the cellular stress induced by drugs. To this end, a measurement protocol, based on the integration of micro-porous supports with OECTs, was developed, that allows to monitor the viability of cells in response to drugs. Cellular stress was monitored by analyzing the electrical response of OECTs, once placed in contact with cells forming a barrier tissue. This application is aimed to develop a point-of-care diagnostic system for in situ and real-time sensing of the viability of cancer or normal cell in response to specific drugs. Finally, Chapter 6 gives an outlook and conclusive remarks on the results achieved in this work. Perspectives and speculation on the future developments and achievements of Organic Bioelectronics are provided.