Organic Bioelectronics Development in Italy: A Review

In recent years, studies concerning Organic Bioelectronics have had a constant growth due to the interest in disciplines such as medicine, biology and food safety in connecting the digital world with the biological one. Specific interests can be found in organic neuromorphic devices and organic transistor sensors, which are rapidly growing due to their low cost, high sensitivity and biocompatibility. This trend is evident in the literature produced in Italy, which is full of breakthrough papers concerning organic transistors-based sensors and organic neuromorphic devices. Therefore, this review focuses on analyzing the Italian production in this field, its trend and possible future evolutions

A Study of Biomedical Sensors Based on Layered Semiconductors: From Characteristics to Nanofabrication Approaches

Among other layered two-dimensional (2D) materials, transition metal dichalcogenides (TMDCs) have revealed their importance in developing novel electronic devices such as field-effect transistors (FETs), optoelectronics, and biomedical sensors. The superior electrical, mechanical, and optoelectronic characteristics, in combination with naturally formed sizable and tunable bandgap of TMDCs, have turned out to be promising for making new biomedical sensors. Despite such a bright prospect, there remain critical scientific and technical gaps that should be filled to enable advanced and practical biomedical sensor applications. Specifically, such gaps include (i) loss of operation stability of MoS2 FET biosensors under wet conditions, (ii) lack of reusability of the electronic biosensors made of TMDCs, and (iii) absence of scalable nanofabrication methods capable of producing well-defined TMDC device patterns. A series of studies presented in this thesis leveraged scientific and technical knowledge to deal with the aforementioned urgent demands and was categorized into three main topics: (i) devise a cycle-wise method for operating MoS2 FET biosensors integrated with a microfluidic channel, which alleviates the liquid-solution-induced issues; (ii) design a new biosensor structure consisting of a bio-tunable nanoplasmonic window and a low-noise few-layer MoS2 photodetector, which can enable highly sensitive, fast, and reusable biosensing processes; (iii) invent scalable nanofabrication and nanomanufacturing approaches capable of producing orderly-arranged TMDCs device channel patterns at designated locations on a target substrate. The presented works have engineered layered semiconductors and device structures based on the scientific knowledge and device physics to realize practical and functional TMDC-based biomedical devices. Additionally, the nanofabrication methods invented in this thesis work could be further developed into cost-efficient and scalable nanomanufacturing techniques that will speed up the development of a wide variety of new device applications made of layered semiconductors.PHDMechanical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/163205/1/bhryu_1.pd

SiNW-based Biosensors for Profiling Biomarkers in Breast Tumor Tissues

Breast cancer is the most common life-threatening malignancy in women of most developed countries today, with approximately 200,000 new cases diagnosed every year. About 30% of these cases progress to metastatic disease and death. Considering that one-third of these cancer deaths could be decreased if detected and treated early, new strategies for early breast cancer detection are needed to improve the efficacy of current diagnostics. The sensitive analysis of proteins such as breast cancer biomarkers has become the focus of intensive research due to its relevance to tumor diagnosis. However, the state-of-the-art diagnostic tools still lack the level of resolution needed for the detection of biomarkers at the very early stage of the disease, when treatments have more probability of success, and when protein concentration in tumor tissue is still very low. Nanotechnologies have shown great potential for the development of high-sensitive, portable devices for clinical applications. In particular, SiNWs with their unique properties such as the high surface-to-volume ratio and size, combined with the specificity of immune-sensing, are natural candidates for the fabrication of nanosensors. Thanks to their compatibility with conventional CMOS technology, SiNWs have been incorporated in standard FETs. In biosensing, SiNW-FETs have been shown a promising method for the label-free detection of trace amounts of biomolecules. However, detection of Antigen using Antibody immobilized SiNW-FETs is limited by ionic screening effects that reduce the sensor responsiveness and limit their applicability in tumor tissue. Here, we propose novel SiNW-based biosensing strategies with the aim of overcoming current sensitivity limitations of conventional SiNW-FET biosensors for the detection of breast cancer biomarkers in real human samples. Specifically, we address this goal by investigating two different approaches of biosensing. In the first method, we push the sensitivity of SiNW-FETs to their limits by proposing an alternative way of doing sensing in dry conditions. We show that in-air electrical measurements of Ab-Ag binding have the big advantage of increased Debye screening length in non-bulk solutions, and enable highly sensitive and specific measurements in breast tumor extract. Then, we present a completely novel biosensing paradigm that shows, for the first time, the use of memristive effects in fabricated SiNWs for biodetection purposes. This novel detection method has been named Voltage Gap (VoG)-biosensing as it is based on the changes of the VoG parameter, observed in the hysteretic characteristic of memristive devices, as a function of biomolecules. In this research, we demonstrate the use of the memristive-based VoG effect in Schottky Barrier SiNWs for the high-resolution sensing of ionic and biological species both in ideal buffer solutions and in tumor tissue extracts. Moreover, we propose an original theory enabling the physical interpretation and prediction of the mechanisms underlying the VoG-biosensing method in memristive devices. Finally, we demonstrate the potential of our system for future integration in a multi-panel VoG-biosensing platform. We fabricated a PDMS microfluidics enabling selective and high-quality functionalization of the NWs. We also realized a CMOS readout circuit for multiplexed VoG acquisition. The simulations demonstrate the feasibility of the approach and the potential for the integration of the reader with a portable and automated biosensing platform. Microfluidics and VoG reader will enable fast, concurrent detection ofmultiple angiogenic and inflammatory ligands in tumor tissue. This will highly improve the level of knowledge of the cancer disease by capturing the heterogeneity and the complexity of the tumor microenvironment, thus leading to novel opportunities in breast cancer diagnosis

Biosensors for Biomolecular Computing: a Review and Future Perspectives

Biomolecular computing is the field of engineering where computation, storage, communication, and coding are obtained by exploiting interactions between biomolecules, especially DNA, RNA, and enzymes. They are a promising solution in a long-term vision, bringing huge parallelism and negligible power consumption. Despite significant efforts in taking advantage of the massive computational power of biomolecules, many issues are still open along the way for considering biomolecular circuits as an alternative or a complement to competing with complementary metal–oxide–semiconductor (CMOS) architectures. According to the Von Neumann architecture, computing systems are composed of a central processing unit, a storage unit, and input and output (I/O). I/O operations are crucial to drive and read the computing core and to interface it to other devices. In emerging technologies, the complexity overhead and the bottleneck of I/O systems are usually limiting factors. While computing units and memories based on biomolecular systems have been successfully presented in literature, the published I/O operations are still based on laboratory equipment without a real development of integrated I/O. Biosensors are suitable devices for transducing biomolecular interactions by converting them into electrical signals. In this work, we explore the latest advancements in biomolecular computing, as well as in biosensors, with focus on technology suitable to provide the required and still missing I/O devices. Therefore, our goal is to picture out the present and future perspectives about DNA, RNA, and enzymatic-based computing according to the progression in its I/O technologies, and to understand how the field of biosensors contributes to the research beyond CMOS

Silicon-based Integrated Microarray Biochips for Biosensing and Biodetection Applications

The silicon-based integrated microarray biochip (IMB) is an inter-disciplinary research direction of microelectronics and biological science. It has caught the attention of both industry and academia, in applications such as deoxyribonucleic acid (DNA) and immunological detection, medical inspection and point-of-care (PoC) diagnosis, as well as food safety and environmental surveillance. Future biodetection strategies demand biochips with high sensitivity, miniaturization, integration, parallel, multi-target and even intelligence capabilities. In this chapter, a comprehensive investigation of current research on state-of-the-art silicon-based integrated microarray biochips is presented. These include the electrochemical biochip, magnetic tunnelling junction (MTJ) based biochip, giant magnetoresistance (GMR) biochip and integrated oscillator-based biochip. The principles, methodologies and challenges of the aforementioned biochips will also be discussed and compared from all aspects, e.g., sensitivity, fabrication complexity and cost, compatibility with silicon-based complementary metal-oxide-semiconductor (CMOS) technology, multi-target detection capabilities, signal processing and system integrations, etc. In this way, we discuss future silicon-based fully integrated biochips, which could be used for portable medical detection and low cost PoC diagnosis applications

Rapid prototyping of 3D Organic Electrochemical Transistors by composite photocurable resin

Rapid Prototyping (RP) promises to induce a revolutionary impact on how the objects can be produced and used in industrial manufacturing as well as in everyday life. Over the time a standard technique as the 3D Stereolithography (SL) has become a fundamental technology for RP and Additive Manufacturing (AM), since it enables the fabrication of the 3D objects from a cost-efective photocurable resin. Eforts to obtain devices more complex than just a mere aesthetic simulacre, have been spent with uncertain results. The multidisciplinary nature of such manufacturing technique furtherly hinders the route to the fabrication of complex devices. A good knowledge of the bases of material science and engineering is required to deal with SL technological, characterization and testing aspects. In this framework, our study aims to reveal a new approach to obtain RP of complex devices, namely Organic Electro-Chemical Transistors (OECTs), by SL technique exploiting a resin composite based on the conductive poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) and the photo curable Poly(ethylene glycol) diacrylate (PEGDA). A comprehensive study is presented, starting from the optimization of composite resin and characterization of its electrochemical properties, up to the 3D OECTs printing and testing. Relevant performances in biosensing for dopamine (DA) detection using the 3D OECTs are reported and discussed too

Organic Electrochemical Transistors

Organic electrochemical transistors (OECTs) leverage ion injection from an electrolyte into an organic semiconductor film to yield compelling advances in biological interfacing, printed logic circuitry and neuromorphic devices. Their defining characteristic is the coupling between electronic and ionic charges within the volume of an organic film. In this review we discuss the mechanism of operation and the materials that are being used, overview the various form factors, fabrication technologies and proposed applications, and take a critical look at the future of OECT research and development

Current nanotechnology advances in diagnostic biosensors

Current diagnostics present challenges that are imposed by increased life expectancy in the worldwide population. These challenges are related, not only to satisfy the need for higher performance of diagnostic tests, but also to the capacity of creating pointâ ofâ care, wearable, multiplexing and implantable diagnostic platforms that will allow early detection, continuous monitoring and treatment of health conditions in a personalized manner. These health challenges are translated into technological issues that need to be solved with multidisciplinary knowledge. Nanoscience and technology play a fundamental role in the development of miniaturized sensors that are cheap, accurate, sensitive and consume less power. At nanometre scale, these materials possess higher volumeâ toâ surface ratio and display novel properties (composition, charge, reactive sites, physical structure and potential) that are exploited for sensing purposes. These nanomaterials can therefore be integrated into diagnostic sensing platforms allowing the creation of novel technologies that tackle current health challenges. These nanomaterialâ enhanced sensors are extremely diverse, since they use numerous types of materials, nanostructures and detection modes for a multitude of biomarkers. The purpose of this review is to summarize the current stateâ ofâ theâ art of nanomaterialâ enhanced sensors, emphasizing and discussing the diagnostic challenges that are addressed by the different engineering and nanotechnology approaches. This review also aims to identify the drawbacks of nanomaterialâ enhanced sensors, as well as point out future developmental directions.This research was funded by FCT- FUNDAÇÃO PARA A CIÊNCIA E TECNOLOGIA, grant numbers: PTDC/EMD-EMD/31590/2017 and PTDC/BTM-ORG/28168/2017