| 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. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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