Organic Bioelectronic Devices for Selective BiomarkerSensing: Towards Integration with Living Systems

Abstract: Inorganic materials have been the main players of the semiconductor industry for the pastforty years. However, there has been a continuous interest and growth in the research and inthe application of organic semiconductors (OSCs) as active materials in electronic devices, dueto the possibility to process these materials at low temperature on flexible substrates,fabricate them on large-area, and upscale their fabrication using cost-effective strategies suchas printing. Because of these features, organic electronic devices are rapidly emerging asbiosensors for biomarkers, with a high potential for becoming a high-throughput tool evendeployable at the point-of-care.One of the most used and studied platforms is the organic electrochemical transistor (OECT).OECTs have been largely used as biosensors in order to transduce and amplify electrical signalsor detect biological analytes upon proper functionalization with specific biorecognition units.OECTs can operate at low voltages, are easy to fabricate on different substrates, and arecompatible with the aqueous environment, and can therefore be interfaced with livingsystems, ranging from mammals to plants. The OECT device configuration includes a gateelectrode that modulates the current in the channel through an electrolyte, which can be notonly a buffered solution but even a complex biological fluid. When OECTs are operated asbiosensors, the sensing mechanism relies on the current variation generated from specificreactions with the analyte of interest. These devices are paving the way to the developmentof point-of-care technologies and portable biosensors with fast and label-free detection.Moreover, OECTs can help to reveal new biological insight and allow a better understandingof physiological processes.During my PhD, I focused on design, fabrication, and validation of different OECT-basedbiosensors for the detection of biomarkers that are relevant for healthcare applications, thusshowing their high potential as a proper sensing platform. We developed sensors towardsdifferent analytes, ranging from small molecules to proteins, with ad hoc designed materialsstrategies to endow the device with selectivity towards the species of interest. Most notably,I also demonstrated the possibility of integrating OECTs in plants, as an example of interfacingthese biosensors with living systems. In the first two papers, we developed screen printedOECTs, presenting PEDOT:PSS as the semiconducting material on the channel. In the first case,3the device also featured a PEDOT:PSS gate electrode which was further functionalized withbiocompatible gelatin and the enzyme urease to ensure selectivity toward the analyte ofinterest, namely urea. The biosensor was able to monitor increasing urea concentrations witha limit of detection of 1 μM. In the second paper the screen-printed carbon gate electrodewas first modified with platinum and then we ensured selectivity towards the analyte uricacid, a relevant biomarker for wound infection, by entrapping urate oxidase in a dual-ioniclayerhydrogel membrane to filter out charged interfering agents. The biosensor exhibited a4.5 μM limit of detection and selectivity even in artificial wound exudate. In the third paperwe designed an interleukin-6 (IL6) OECT based biosensor able to detect the cytokine down tothe pM regime in PBS buffer. The mechanism of detection relied on the specific bindingbetween an aptamer, used as sensing unit on the gate electrode, and the IL6 in solution,allowing for detection ranging from physiological to pathological levels.In the last two papers we developed OECT based biosensors to be interfaced with the plantworld. In the fourth paper we presented a glucose sensor, based on the enzyme glucoseoxidase (GOx) to detect glucose export from chloroplasts. In particular, we demonstrated realtimeglucose monitoring with temporal resolution of 1 minute in complex media. In the fifthpaper, we developed implantable OECT-based sugar sensors for in vivo real-time monitoringof sugar transport in poplar trees. The biosensors presented a multienzyme-functionalizedgate endowing the device with specificity towards glucose and sucrose. Most notably, theOECT sensors did not cause a significant wound response in the plant, allowing us todemonstrate that OECT-based sensors are attractive tools for studying transport kinetics inplants, in vivo and real-time.

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