| 1. |
- Cherian, Dennis, 1989-
(författare)
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Expanding the versatility and functionality of iontronic devices
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Biological systems rarely use electrons as signal regulators, most of the transport and communication in these system utilize ions. The discovery of conjugated polymers and polyelectrolytes and their unique properties of mixed ionic electronic properties opened the possibility of using these in the domain of bioelectronics, which paved the way for the field of organic bioelectronics. After the introduction of the organic electronic ion pump (OEIP) in 2007, which utilizes both the ionic properties of conjugated polymers and polyelectrolytes, the new field of “iontronics” evolved. TheOEIP is an organic polymer-based delivery system based on electrophoretic transport of biologically relevant and ionically charged species, without fluid flow and with high spatial, temporal, and dosage precision. These devices have been extensivelystudied for the past 14 years and have found numerous demonstrations in in vivo and in vitro delivery of bio-relevant ions for therapeutic application. This has, in parallel, resulted in the development of custom materials for ion exchange membranes (IEMs) within the OEIP.This thesis focuses on IEMs and device development of OEIPs. Specific focus is given to process development through device design and fabrication through conventional and unconventional technologies. Conventional technologies include microfabrication through photolithography, etching, and thin-film evaporation. Unconventional fabrication techniques include screen printing, inkjet printing, stencil, and laser patterning. In this thesis, we have also scouted a new area of research to utilize the ion-selective properties of polyelectrolytes. Here we discuss a new ion detection technique using IEMs and ion transport based on diffusion coefficients and impedance measurement at a specific frequency using impedance spectroscopy for faster ion detection with low voltage (1–40 V) and liquid-flow-free transport. Further exploring the area of IEMs, we have realized that less attention has been given to stretchable IEMs, even though such materials could find enormous applications in the field of organic bioelectronics and can be used in association with many stretchable electronics applications like stretchable displays and energy storage devices. Current IEMs lack the conformability and stretchability to be used for implantable applications, e.g., including lungs, heart, muscle, soft or brain implants, joints, etc. Keeping this in mind we also discuss our approach for the development of a stretchable IEM. Finally, we focus on developing a hybrid fabrication protocol of flexible OEIPs with micropatterning techniques and inkjet-printed membranes. These OEIPs were fabricated and the functionality was validated by the cell response after the delivery of a nerve-blocking agent to cells in vitro. To date, OEIPs have been fabricated by micropatterning and labor-intensive manual techniques, impeding the budding application areas of this propitious technology. To address this issue, a novel approach to the fabrication of the OEIPs using screen-printing technology is also explored in this thesis. In summary, we were able to successfully explore the field of ion-exchange membranesand put forward a new technique for ion detection and stretchable IEMs for future applications. Fabrication of OEIPs was also examined which resulted in the development of a hybrid fabrication protocol with inkjet printing for OEIPs and a robust fully screen printed OEIPs with high manufacturing yield (>90%) for industrial-scale manufacturing.
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| 2. |
- Li, Changbai
(författare)
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Advances in bioelectronic interfaces through controlled polymerization of tri-thiophene monomers
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the domain of conventional electronics which are integrated into our daily lives, electrons predominantly serve as charge carriers. In contrast, biological systems primarily utilize ions and molecules of various sizes for signal transmission. This communication gap has been effectively bridged by the advent of conducting and semiconducting organic polymers, which uniquely exhibit combined electronic and ionic conductivity. These materials have become invaluable in translating signals between electronic and biological systems, giving rise to the field of organic bioelectronics. This field now offers a flexible platform that develops tools for biological recording and regulation, with potential applications extending from life sciences to clinical applications. This thesis explores advancements in organic bioelectronics, focusing on the development of organic electrochemical transistors (OECTs) based on conducting polymers and the development of organic conductors composed of conductive hydrogels, through controlled polymerization of tri-thiophene monomers. We began by investigating the electrically driven polymerization of the water-soluble tri-thiophene monomer called ETE-S. Our analysis demonstrates how alterations in monomer concentrations can affect the monomer aggregation in solution and the electrical properties of the resultant conducting polymer films, which are crucial for the potential development of neuromorphic devices and other bioelectronic applications. Additionally, we investigated the electrically driven copolymerization of the water-soluble tri-thiophene monomers with two distinct sidechains, including ETE-S and ETE-PC. This study demonstrated that the onset potential of electropolymerization process and threshold voltage of the resultant OECT devices can be influenced by regulating monomer blend ratios, thereby enhancing the functionality of OECTs for bioelectronic applications. Furthermore, enzymatic polymerization of a water-soluble tri-thiophene monomer ETE-S was employed to develop conductive hydrogel-base organic conductors for interfacing with biological systems. We developed a novel method to fabricate cytocompatible and conductive hydrogels suitable for three-dimensional (3D) cell culture and 3D bioprinting. These conductive hydrogels possess tissue-like mechanical properties with mixed ionic and electronic conductivity, providing innovative strategies to utilize electrical signals to modulate cell behavior within a native-like microenvironment. To expand our understanding of electrophysiology, we also developed an on-skin conductive hydrogel using enzymatic polymerization of monomer ETE-S for electrophysiological applications. This conductive hydrogel is ionically crosslinked to enable liquid-to-gel transition to dynamically conform to skin topographies, facilitating the accuracy and reliability of electrophysiological recordings. Overall, this thesis contributes to the field of organic bioelectronics by exploring the potential of OECTs for specialized bioelectronic applications and the development of conductive hydrogels for 3D cell culture and electrophysiological recordings, achieved through controlled polymerization of tri-thiophene monomers. The findings provide a foundation for future research into advanced bioelectronic interfaces, which have the potential to enhance biomedical technologies and therapeutic methods.
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| 3. |
- Nissa, Josefin, 1987-
(författare)
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Interacting with biological membranes using organic electronic devices
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many physiological processes are reliant on activities in the cell membrane. These activities are of great importance to our well-being since they allow the cells to respond to their environment and communicate with each other to function as tissues and organs. In this thesis the use of organic electronic devices to interface with cell membranes has been explored. Organic electronics are especially suited for the task given their ability to transduce ionic to electronic signals. Four scientific papers are included in the thesis, where organic electronic devices are used together with living cells and supported lipid bilayers (SLB). In the first paper a ferroelectric cell release surface is presented. Release of cells cultured on the surface was induced by a polarization change in the ferroelectric polymer. This non-enzymatic release method was developed primarily for treatment of severe burns.The remaining three papers strive to combine lipid bilayers and the conjugated polymer poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) in biosensors. The target device is an organic electrochemical transistor (OECT) functionalized with a supported lipid bilayer. Several aspects of the integration are explored, including promotion of vesicle fusion onto PEDOT:PSS and optimization of OECT design and biasing conditions for sensing. For SLB formation on PEDOT:PSS two different silica material systems, one PEDOT:PSS/silica composite and one mesoporous silica film, were evaluated with respect to electrical properties and quality of the resulting bilayer. The electrical properties were found to be similar, but the quality of the bilayer was better on the mesoporous silica film.In the last two papers the focus is on optimization of OECTs for sensing purposes. Biasing conditions for operation at high transconductance were identified, as well as design principles for large sensor output in impedance sensing.
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| 4. |
- Roy, Arghyamalya, 1992-
(författare)
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Bioelectronic Devices for Targeted Drug Delivery and Monitoring of Microbial Electrogenesis
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Despite a range of pain therapies available in the market, 70% of patients report so-called “breakthrough pain”. Coupled with global issues like opioid crisis, there is a clear need for advanced therapies and technologies for pain management. In this thesis we aim to develop a novel pain management therapy based on precise, fluid-flow-free delivery of anesthetic drugs directly to the peripheral nervous system (PNS) using organic electronic ion pumps (OEIPs). OEIPs are devices that can transport charged drug molecules through a permselective ion exchange membrane (IEM) under an applied electric field. In this work we used primary dorsal root ganglion (DRG) neurons as an in vitro PNS model system for neuropathic pain. The IEM was made up of custom synthesized hyberbranched polyglycerols (HPGs), which enabled the delivery of large aromatic anesthetic drug such as bupivacaine for the first time in an OEIP. Bupivacaine is a common local nerve blocker which if delivered to DRGs effectively blocks their neuronal activity which in turn blocks the pain signal to travel to the central nervous system (CNS) thereby blocking the sensation of pain. Two types of OEIP devices were fabricated and characterized in this context: capillary-based OEIPs with a probe-like form factor, and inkjet-printed flexible OEIPs with a potential towards implantable form factor. The results showed that both types of OEIP devices could deliver bupivacaine locally (delivery radius ~ 75 µm) to DRG neurons at concentrations close to 40000 times lower than the bulk/bolus means. The results demonstrated that OEIPs could achieve long-lasting and reversible nerve blockage without causing tissue damage or systemic side effects. These studies lay the foundation for future demonstrations of “iontronic” PNS pain relief in living/awake animals. On the other end of the spectrum, most of today’s modern communication is based upon our understanding of how electrons move through semiconductors. This allows one to mediate the flow of electrons by designing complex integrated circuits in the form of microchips which gives rise to smart devices such as mobile phones and computers. Likewise, in many organism’s electron transfer plays a critical role in metabolic processes in eukaryotes, which includes animals all the way down to microbes. In most of these metabolic processes, the role of the final electron acceptor is played by oxygen (aerobic respiration). However, there are few families of bacterial cells that we know today have evolved in special ways allowing them to respire or “breathe” through metals/metal oxides when exposed to anaerobic conditions. In electromicrobiology, this is termed as extracellular electron transfer (EET), wherein the microbes shuttle electrons from inside of their cells to the outside, in presence of favorable extracellular electron acceptors. The EET process has thus been exploited in various microbial electrochemical systems (MESs) such as microbial fuel cells (MFCs), biosensors, and bio-photovoltaic cells to name a few. In this thesis, we have carried out a detailed study examining the EET process in MESs and ways to amplify such signals in broadly two major approaches: Bioelectrochemical and device optimization. Under bioelectrochemical means, we have shown that we can amplify EET signal of exoelectrogens such as Shewanella oneidensis MR-1 in a standard microbial bioreactor set up containing fumarate (a common carbon food source) by up to 50x times without the excess cell growth in the reactor. This study helped to unravel few unknown mysteries of the EET and bust few of its well-studied myths in the process. However, to record EET, traditionally one still requires large area/volume of electrodes with sufficiently high concentration of bacteria to remain well above the threshold signal-to-noise ratio. So under device optimization route, we combined S.oneidensis with an electrochemical transistor termed as Organic Microbial Electrochemical Transistor (OMECT). With OMECT we successfully monitored and amplified EET events from small number of microbial cells on a microscale area (500 µm x 500 µm) in real time without the need big/bulky/expensive signal amplifying instruments. Interestingly, the OMECT platform also revealed an order of magnitude faster EET response of S. oneidensis MR-1 to lactate compared to studies using classical electrochemical approaches thus underlying one of the major advantages of the miniaturized bioelectronic device.
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| 5. |
- Abrahamsson, Tobias, 1991-
(författare)
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Synthetic Functionalities for Ion and Electron Conductive Polymers : Applications in Organic Electronics and Biological Interfaces
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the search for understanding and communicating with all biological systems, in humans, animals, plants, and even microorganisms, we find a common language of all communicating via electrons, ions and molecules. Since the discovery of organic electronics, the ability to bridge the gap and communicate be-tween modern technology and biology has emerged. Organic chemistry pro-vides us with tools for understanding and a material platform of polymer electronics for communication. Such insights give us not only the ability to observe fundamental phenomenon but to actively design and construct materials with chemical functionalities towards better interfaces and applications. Organic electronic materials and devices have found their way to be implemented in the field of medicine for diagnostic and therapeutic purposes, but also in water purification and to help tackle the monumental task in creating the next generation of sustainable energy production and storage. Ultimately it’s safe to say that organic electronics are not going to replace our traditional technology based on inorganic materials but rather the two fields can find a way to complement each other for various purposes and applications. Compared to conventional silicon based technology, production of carbon-based organic electronic polymer materials are extremely cheap and devices can even be made flexible and soft with great compatibility towards biology. The main focus of this thesis has been developing and synthesizing new types of organic electronic and ionic conductive polymeric materials. Rational chemical design and modifications of the materials have been utilized to introduce specific functionalities to the materials. The functionalities serving the purpose to facilitate ion and electron conductive charge transport for organic electronics and with biological interface implementation of the polymer materials. Multi-functional ionic conductive hyperbranched polyglycerol polyelectrolytes (dendrolytes) were developed comprising both ionically charged groups and cross-linkable groups. The hyperbranched polyglycerol core structure of the material possesses a hydrophilic solvating platform for both ions and maintenance of solvent molecules, while being a biocompatible structure. Coupled with the peripheral charged ionic functionalities of the polymer, the dendrolyte materials are highly ionic conductive and selective towards cationic and anionic charged atoms and large molecules when implemented as ion-exchange membranes. Homogenous ion-exchange membrane casting has been achieved by the implementation of cross-linkable functionalities in the dendrolytes, utilizing robust click-chemistry for efficient micro and macro fabrication processing of the ion-ex-change membranes for organic electronic devices. The ion-exchange membrane material was implemented in electrophoretic drug delivery devices (organic electronic ion pumps), which are used for delivery of ions and neurotransmitters with spatiotemporal resolution and are able to communicate and be used for therapeutic drug delivery purposes in biological interfaces. The dendrolyte materials were also able to form free-standing membranes, making it possible for implementation in fuel cell and desalination purposes. Trimeric conjugated thiophene pre-polymer structures were also developed in the thesis and synthesized for the purpose of implementation of the material in vivo to form electrically conductive polymer structures, and in such manner to be able to create electrodes and ultimately to connect with the central nervous system. The conjugated pre-polymers being both water soluble and enzymatically polymerizable serve as a platform to realize such a concept. Also, modifying the trimeric structure with cross-linkable functionality created the capability to form better interfaces and stability towards biological environments.
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| 6. |
- Arbring Sjöström, Theresia, 1987-
(författare)
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Organic Bioelectronics for Neurotransmitter Release at the Speed of Life
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The signaling dynamics in neuronal networks includes processes ranging from lifelong neuromodulation to direct synaptic neurotransmission. In chemical synapses, the time delay it takes to pass a signal from one neuron to the next lasts for less than a millisecond. At the post-synaptic neuron, further signaling is either up- or down-regulated, dependent on the specific neurotransmitter and receptor. While this up- and down-regulation of signals usually runs perfectly well and enables complex performance, even a minor dysfunction of this signaling system can cause major complications, in the shape of neurological disorders. The field of organic bioelectronics has the ability to interface neurons with high spatiotemporal recording and stimulation techniques. Local chemical stimulation, i.e. local release of neurotransmitters, enables the possibility of artificially altering the chemical environment in dysfunctional signaling pathways to regain or restore neural function. To successfully interface the biological nervous system with electronics, a range of demands must be met. Organic bioelectronic techniques and materials are capable of reaching the demands on the biological as well as the electronic side of the interface. These demands span from high performance biocompatible materials, to miniaturized and specific device architectures, and high dose control on demand within milliseconds.The content of this thesis is a continuation of the development of organic bioelectronic devices for neurotransmitter delivery. Organic materials are utilized to electrically control the dose of charged neurotransmitters by translating electric charge into controlled artificial release. The first part of the thesis, Papers 1 and 2, includes further development of the resistor-type release device called the organic electronic ion pump. This part includes material evaluation, microfluidic incorporation, and device design considerations. The aim for the second part of this thesis, Papers 3 and 4, is to enhance temporal performance, i.e. reduce the delay between electrical signal and neurotransmitter delivery to corresponding delay in biological neural signaling, while retaining tight dosage control. Diffusion of neurotransmitters between nerve cells is a slow process, but since it is restricted to short distances, the total time delay is short. In our organic bioelectronic devices, several orders of magnitude in speed can be gained by switching from lateral to vertical delivery geometries. This is realized by two different types of vertical diodes combined with a lateral preload and waste configuration. The vertical diode assembly was further expanded with a control electrode that enables individual addressing in each of several combined release sites. These integrated circuits allow for release of neurotransmitters with high on/off release ratios, approaching delivery times on par with biological neurotransmission.
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| 7. |
- Dufil, Gwennaël, 1995-
(författare)
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Living biohybrid systems via in vivo polymerization of thiophene oligomers
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Life is the result of a multitude of electrical signals which drives our nervous system but also accomplishes a cascade of electrochemical reactions. In the 18th century, Lucia Galeazzi and Luigi Galvani got the idea to stimulate frog legs with electrodes. This first step into the world of bioelectronics showed that electronic systems were able to communicate with living organisms through electrical stimulation, as well as by recording electrical signals from organisms. Until the end of the 20th century, the field of bioelectronics kept progressing using metal electrodes. This class of material inherently exhibits a high conductivity from their dispersed cloud of shared electrons. However, an obvious physical mismatch occurs when inserting metal electrodes inside a living organism. Since these materials are not as soft as living tissues, internal damage followed by an immune response impacts the impedance of such probes.In the late 80s', the large-scale commercialization of water processable conducting polymers brought a new paradigm in the choice of electronic material for bioelectronics devices. Compared to metals, conducting polymers are composed of semi-crystalline blocks that interact through electrostatic forces. These soft structures make these materials permeable to aqueous solutions, which allow the introduction of ionic species in the vicinity of the polymer backbone. Ions close to the polymer backbone can tune the conductivity of the material creating a unique ion/electron dialogue that increases the electronic signal resolution. Additionally, these soft structures considerably reduce scaring effects and therefore enable the devices to trigger lower immune responses. Conducting polymers could also be directly inserted within living tissues to create electronic platforms inside a host. Living organisms with new material properties could unravel new functions such as collecting electrophysiological data without surgery.Plants are living organisms that made their way out of the ocean and conquered most of the available land on earth. Saying that plants are good climate controllers is a euphemism since plants are legitimately the organisms that have settled the climate conditions for the development of more advanced life forms. Plant biohybrid is a new technological concept where plants are not only seen for their nutritious or environmental aspect but also as devices that can record and transfer information about their local environmental conditions. Such data could be used in a positive feedback loop to improve the production yield of crops or understand the underlying communication mechanism that occurs between plants or with plant micro-biomes. Most of the approaches toward plant biohybrids nowadays focus on nanomaterials that act as fluorescent probes in leaves and detect analytes from plants' local environment.In this thesis, we push forward a plant biohybrid strategy that instead uses conducting polymers as vectors to build conductors inside plants with the aim to build electrochemical platforms that could be used for applications such as energy storage, sensing, and energy production. Works developed in this thesis are going in an array of directions that aims for the better integration of electronic platforms in living systems with more focus on plants.We first identified a plant enzymatic mechanism that triggers the polymerization of a thiophene oligomer, namely ETE-S in vivo and in vitro. Such plant enzymatic pathways can then be reused to develop electronic systems in plantae without additional reagents. In the next work, we presented the synthesis of three new oligomers called ETE-N, EEE-S, and EEE-N that have a similar architecture compared to ETE-S but with different chemical moieties such as a different ionic side chain or an EDOT instead of thiophene in the middle position of the oligomer. We then demonstrated the effective enzymatic polymerization of these oligomers both in vivo and in vitro and how the resulting polymers' optoelectronic and tissue integrations properties differ. Towards even more versatility, we demonstrated that this electronic integration in vivo was also observed in the case of an animal: the freshwater hydra polyp. The polymerization was observed mostly in differentiated cells from the gastric column of the animal that normally secretes an adhesive used to fix the animal underwater. P(ETE-S) was incorporated in this glue that we managed to characterize using electrochemical methods. Lastly, we performed demonstrations of electrochemical applications with a plant root system. By dipping several roots in an ETE-S solution, we created a network of conducting roots that can effectively store charge as a capacitor with performance comparable to what is classically obtained with conducting polymers. In addition, we modified roots with two different surface modification concepts to make them specific to glucose oxidation: the first method uses a traditional redox hydrogel with a crosslinker and glucose oxidase. The second one uses the embedment of a glucosespecific enzyme inside the p(ETE-S) layer during its formation. These devices are presented as possible new solutions for environmental glucose sensors that could collect current from the environment and store it in neighbouring capacitive roots.Overall, this thesis shows that the enzymatic activity of living systems can be used from an engineering point of view as part of a deposition methods for the development of biohybrid applications.
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| 8. |
- Jakešová, Marie, 1991-
(författare)
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Wireless Bioelectronic Devices Driven by Deep Red Light
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The use of electronic devices in medical care is one of the main targets of precision medicine. The field of bioelectronic medicine uses electronic devices to diagnose or treat diseases and disorders in a complementary or alternative way to chemical drugs. It has been more than sixty years since the world’s first implantable battery-driven cardiac pacemaker was implanted here in Sweden. Since then, electronic therapies have been implemented for neurological disorders such as Parkinson’s disease, epilepsy, sensory and motor function restoration, and many more. However, electronics can also be used for delivery of conventional drugs in a more controlled, localized, and specific fashion.Therapeutic utility and patient comfort are maximized when the devices are as minimally invasive as possible. The most important milestone in the development of the cardiac stimulator was making it wireless. The early versions of the device required bulky parts to be placed outside of the body with transcutaneous electrical leads to the target site which led to high infection risk and frequent failures. To date, batteries remain the most common way to power implantable electronics. However, their large size and the necessity for replacement surgeries makes the technology relatively invasive. Alternative approaches to wireless power transfer are thus sought after. The most promising technologies are based on electromagnetic, ultrasound, or light-coupling methods. The aim of this thesis is to utilize tissue-penetrating deep red light for powering implantable devices. The overarching concept is an organic photovoltaic based on small molecule donor-acceptor bilayer junctions, which allows for ultrathin, flexible, minimally-invasive devices. Within this thesis, the photovoltaic device was utilized in two ways. Firstly, the photovoltaics are fabricated to act as an integrated driver for other implantable electronic components: 1) an organic electronic ion pump for acetylcholine delivery; 2) a depth-probe microelectrode stimulation device for epilepsy applications. Secondly, an alternative device, the organic electrolytic photocapacitor, is formed by replacing one of the solid electrodes by an electrolytic contact, thus yielding a minimalistic device acting as a direct photoelectrical stimulator. Within the thesis, the photocapacitive stimulation mechanism is validated by studying voltage-gated ion channels in a frog oocyte model. Next, two lithography-based patterning techniques are developed for fabricating these devices with better resolution and on flexible substrates suitable for in vivo operation. Finally, a chronic implant is demonstrated for in vivo sciatic nerve stimulation in rodents. The end result of this thesis is a series of novel device concepts and methods for stimulation of the nervous system using deep red light.
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| 9. |
- Seitanidou, Maria, 1985-
(författare)
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Overcoming Limitations of Iontronic Delivery Devices
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Organic electronic devices are considered as one of the best candidates to replace conventional inorganic electronic devices due to their electronic conductive functionality, low-cost production techniques, the ability to tune their optical and electronic properties using organic chemistry, and their mechanical flexibility. Moreover, these systems are ideal for bioelectronic applications due to their softness, biocompatibility, and most importantly, their electronic and ionic transport. Indeed, these materials are compatible with biological tissues and cells improving the signal transduction between electronic devices and electrically excitable cells. As ions serve as one of the primary signal carriers of cells, they can selectively tune a cell’s activity; therefore, an improved interface between electronics and biological systems can offer several advantages in healthcare, e.g. the development of efficient drug delivery devices. The main focus of this thesis is the development of electronic delivery devices. Electrophoretic delivery devices called organic electronic ion pumps (OEIPs) are used to electronically control the delivery of small ions, neurotransmitters, and drugs with high spatiotemporal resolution. This work elucidates the ion transport processes and phenomena that happen in the ion exchange membranes during ion delivery and clarifies which parameters are crucial for the ion transport efficiency of the OEIPs. This thesis shows a systematic investigation of these parameters and indicates new methods and OEIP designs to overcome these challenges. Two novel OEIP designs are developed and introduced in this thesis to improve the local ion transport while limiting side effects. OEIPs based on palladium proton trap contacts can improve the membrane permselectivity and optimize the delivery of γ-aminobutyric acid (GABA) neurotransmitters at low pH while preventing any undesired pH changes from proton transport in the biological systems. And OEIPs based on glass capillary fibers are developed to overcome the limitations of devices on planar substrates, related to more complex and larger biologically relevant ion delivery with low mobility for implantable applications. This design can optimize the transport of ions and drugs such as salicylic acid (SA) at low concentrations and at relatively much higher rates, thereby addressing a wider range of biomedically relevant applications and needs.
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| 10. |
- Diacci, Chiara, 1992-
(författare)
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Organic Bioelectronic Devices for Selective Biomarker Sensing : Towards Integration with Living Systems
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inorganic materials have been the main players of the semiconductor industry for the past forty years. However, there has been a continuous interest and growth in the research and in the application of organic semiconductors (OSCs) as active materials in electronic devices, due to 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 such as printing. Because of these features, organic electronic devices are rapidly emerging as biosensors for biomarkers, with a high potential for becoming a high-throughput tool even deployable 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 signals or detect biological analytes upon proper functionalization with specific biorecognition units. OECTs can operate at low voltages, are easy to fabricate on different substrates, and are compatible with the aqueous environment, and can therefore be interfaced with living systems, ranging from mammals to plants. The OECT device configuration includes a gate electrode that modulates the current in the channel through an electrolyte, which can be not only a buffered solution but even a complex biological fluid. When OECTs are operated as biosensors, the sensing mechanism relies on the current variation generated from specific reactions with the analyte of interest. These devices are paving the way to the development of 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 understanding of physiological processes. During my PhD, I focused on design, fabrication, and validation of different OECT-based biosensors for the detection of biomarkers that are relevant for healthcare applications, thus showing their high potential as a proper sensing platform. We developed sensors towards different analytes, ranging from small molecules to proteins, with ad hoc designed materials strategies 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 interfacing these biosensors with living systems. In the first two papers, we developed screen printed OECTs, presenting PEDOT:PSS as the semiconducting material on the channel. In the first case, the device also featured a PEDOT:PSS gate electrode which was further functionalized with biocompatible gelatin and the enzyme urease to ensure selectivity toward the analyte of interest, namely urea. The biosensor was able to monitor increasing urea concentrations with a limit of detection of 1 µM. In the second paper the screen-printed carbon gate electrode was first modified with platinum and then we ensured selectivity towards the analyte uric acid, a relevant biomarker for wound infection, by entrapping urate oxidase in a dual-ionic-layer hydrogel membrane to filter out charged interfering agents. The biosensor exhibited a 4.5 µM limit of detection and selectivity even in artificial wound exudate. In the third paper we designed an interleukin-6 (IL6) OECT based biosensor able to detect the cytokine down to the pM regime in PBS buffer. The mechanism of detection relied on the specific binding between 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 plant world. In the fourth paper we presented a glucose sensor, based on the enzyme glucose oxidase (GOx) to detect glucose export from chloroplasts. In particular, we demonstrated real-time glucose monitoring with temporal resolution of 1 minute in complex media. In the fifth paper, we developed implantable OECT-based sugar sensors for in vivo real-time monitoring of sugar transport in poplar trees. The biosensors presented a multienzyme-functionalized gate endowing the device with specificity towards glucose and sucrose. Most notably, the OECT sensors did not cause a significant wound response in the plant, allowing us to demonstrate that OECT-based sensors are attractive tools for studying transport kinetics in plants, in vivo and real-time.
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