Organic Electrochemical Transistor for Biological Applications
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Abstract
Bioelectronics is a strong emerging field, bridging the interface of organic electronics with the world of biology. One popular theme has been to use the organic electrochemical transistor (OECT). Its key advantage is the local high amplification at low-voltage operation, offering excellent biocompatibility and ease of fabrication. The OECT has yielded a vast array of promising applications ranging from electrophysiology, by recordings of neural activity of organs, to biosensing, by the detection of analytes and metabolites. A further interesting aspect is the monitoring of cell coverage and cellular health of non-electrogenetic cells, among other for application in drug screening and targeting. The OECT has been shown as a complementary sensor for cell barrier integrity in comparison to traditional techniques such as immunofluorescence, permeability assay and transepithelial electrical resistance measurements. Nevertheless, the reversible control of cell layer opening in a high sensitive and temporal resolution, essential for the use in drug delivery systems, still suffers from deficits. In order to take advantage of the attractive properties of the OECT for biomedical applications as in improved assessment of cell layer integrity, the OECT needs to be further pushed towards greater sensitivity and efficiency to meet the requirements of high-performance biosensing. Therefore, the goal of this work is on the one hand to design OECTs of high performance, and on the other hand to establish efficient methods for improving barrier tissue characterization, by exploiting electrical as well as biological possibilities. The first two chapters focus on material improvements and device physics to create the foundation of OECTs for interfacing biology. Chapter 3 addresses material improvements of PEDOT:PSS as the conductive channel in the OECT, to drive towards high-performance biosensing: Organic solvent treatments, in particular the Post-Treatment method, have been exploited to significantly increase the conductivity of PEDOT:PSS, leading to improved OECT performances on the grounds of a phase segregation in PEDOT:PSS-rich and PSS-rich domains and enhanced structural order. The second part concentrates on alternative device configurations during measurements to increase sensitivity (Chapter 4). Next to the large transconductance towards high-performance biosensing, the sensitivity of ion detection can be increased by connecting the OECT in series with a current generator. The current-driven OECT has been demonstrated to yield the highest value for ion sensitivity, normalized to the supply voltage, ever reported for ion-sensitive transistors. Taking this into account, the following two chapters describe the final interfacing with biological membranes. For efficient biosensing, Chapter 5 pursues at first a classic approach by using an array of electrodes. Impedance spectroscopy studies on PEDOT:PSS-coated electrodes of various sizes, incorporating a cell layer, have demonstrated sensing and non-sensing regimes, depending on the area of the electrode. The determinant is given by the ratio of the impedance of the cell layer, to the impedance of the electrode, which has to be greater than one for biosensing capability. Next to electrodes, the OECT, as an active element, offers the possibility of creating small circuits. In the following drug screening experiments, the combination of the current-driven configuration of the OECT with integration of a cell layer, has led to a greater sensitive and temporal assessment of cell barrier integrity under the influence of toxins. Hydrogen peroxide has been used to induce permanent changes in its integrity (Chapter 6). The last two chapters are dedicated to explore ways to control the ability of the cells forming tissue barriers by external stimuli. To regain more control in a manner of reversible cell opening instead of permanent damages in the last chapter, tight junction modulators, as a form of chemical stimuli, have been investigated for its temporary impact on cell connections of adherent cells (Chapter 7). This issue has been even more intensified by the use of optogenetics tools to control cell-cell interactions with the precise use of light as an optical modulation (Chapter 8). Expressing photoswitchable proteins on the surface of a cell, cell-cell interaction in form of cell opening and closing has been investigated by its activation and inactivation upon light irradiation.