| 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. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- Datta-Chaudhuri, Timir, et al.
(författare)
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The Fourth Bioelectronic Medicine Summit "Technology Targeting Molecular Mechanisms" : current progress, challenges, and charting the future
- 2021
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Ingår i: Bioelectronic medicine. - : BioMed Central. - 2332-8886. ; 7:1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- There is a broad and growing interest in Bioelectronic Medicine, a dynamic field that continues to generate new approaches in disease treatment. The fourth bioelectronic medicine summit "Technology targeting molecular mechanisms" took place on September 23 and 24, 2020. This virtual meeting was hosted by the Feinstein Institutes for Medical Research, Northwell Health. The summit called international attention to Bioelectronic Medicine as a platform for new developments in science, technology, and healthcare. The meeting was an arena for exchanging new ideas and seeding potential collaborations involving teams in academia and industry. The summit provided a forum for leaders in the field to discuss current progress, challenges, and future developments in Bioelectronic Medicine. The main topics discussed at the summit are outlined here.
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