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Controlled Microscopic Formation of Amyloid-Like Aβ Aggregates Using an Organic Electronic Device
Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, The Institute of Technology. (Laboratory of Organic Electronics)ORCID iD: 0000-0002-0302-226X
Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, The Institute of Technology. (Laboratory of Organic Electronics)
Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.ORCID iD: 0000-0002-5582-140X
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Alzheimer’s disease (AD), primarily associated with formation of fibrillar amyloid-beta peptide (Aβ) aggregates in the brain, is one of the most common old-age diseases. It is therefore crucial with an elevated scientific interest in Aβ, and its fundamental properties in a wide sense, to develop efficient methods for early detection and to combat AD. For the development of new techniques, both for AD detection and prevention, researchers are dependent on either tissue samples from deceased patients, animal models or in vitro systems. In vitro systems, such as producing protein aggregates of the Aβ-peptide in a test tube by incubation under denaturing conditions, offers us a simple but rather blunt tool for evaluating aggregation inhibition caused by compounds or to investigate new detection methods. We recently introduced the organic electronic ion pump (OEIP) as a method for creating amyloid-like aggregates at high spatiotemporal control as compared to the resulting aggregates manufactured using regular test tube-conditions. Combined with a fluorescent probe that is specific for the fibrillar aggregated form of misfolded peptides commonly seen in AD, this allowed us to control and to monitor the aggregation of a model peptide system in a highly confined space.

To further elaborate the functionality of the OEIP together with amyloid-specific probes, we here present experiments demonstrating electronically controlled micron sized formation of Aβ-aggregates with morphologies ranging from fine fibers, to bundles of fibers, and thick mesh-like fiber structures. We foresee that the methodology can be implemented in multi array systems that can be utilized for studies of protein aggregation in confined spaces or together with cultured cells, as well as for the development of screening platforms for assessment of molecules influencing the Aβ-aggregation process.

National Category
Polymer Technologies Other Electrical Engineering, Electronic Engineering, Information Engineering Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-110401OAI: oai:DiVA.org:liu-110401DiVA: diva2:745419
Available from: 2014-09-10 Created: 2014-09-10 Last updated: 2017-02-03Bibliographically approved
In thesis
1. Monopolar and Bipolar Membranes in Organic Bioelectronic Devices
Open this publication in new window or tab >>Monopolar and Bipolar Membranes in Organic Bioelectronic Devices
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In the 1970s it was discovered that organic polymers, a class of materials otherwise best know as insulating plastics, could be made electronically conductive. As an alternative to silicon semiconductors, organic polymers offer many novel features, characteristics, and opportunities, such as producing electronics at low costs using printing techniques, using organic chemistry to tune optical and electronic properties, and mechanical flexibility. The conducting organic polymers have been used in a vast array of devices, exemplified by organic transistors, light-emitting diodes, and solar cells. Due to their softness, biocompatibility, and combined electronic and ionic transport, organic electronic materials are also well suited as the active material in bioelectronic applications, a scientific and engineering area in which electronics interface with biology. The coupling of ions and electrons is especially interesting, as ions serve as signal carriers in all living organisms, thus offering a direct translation of electronic and ionic signals. To further enable complex control of ionic fluxes, organic electronic materials can be integrated with various ionic components, such as ion-conducting diodes and transistors.

This thesis reports a background to the field of organic bioelectronic and ionic devices, and also presents the integration of ionic functions into organic bioelectronic devices. First, an electrophoretic drug delivery device is presented, capable of delivering ions at high spatiotemporal resolution. The device, called the organic electronic ion pump, is used to electronically control amyloid-like aggregation kinetics and morphology of peptides, and offers an interesting method for studying amyloids in vitro. Second, various ion-conducting diodes based on bipolar membranes are described. These diodes show high rectification ratio, i.e. conduct ions better for positive than for negative applied voltage. Simple ion diode based circuits, such as an AND gate and a full-wave rectifier, are also reported. The AND gate is intended as an addressable pH pixel to regulate for example amyloid aggregation, while the full-wave rectifier decouples the electrochemical capacity of an electrode from the amount of ionic charge it can generate. Third, an ion transistor, also based on bipolar membranes, is presented. This transistor can amplify and control ionic currents, and is suitable for building complex ionic logic circuits. Together, these results provide a basic toolbox of ionic components that is suitable for building more complex and/or implantable organic bioelectronic devices.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2014. 76 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1620
Keyword
bioelectronics, ionic, ion transport;bipolar membrane, conjugated polymer, amyloid, self-assembly
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:liu:diva-110406 (URN)10.3384/diss.diva-110406 (DOI)978-91-7519-244-4 (ISBN)
Public defence
2014-10-10, K2, Kåkenhus, Campus Norrköping, Linköpings Universitet, Norrköping, 10:00 (English)
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Supervisors
Available from: 2014-09-10 Created: 2014-09-10 Last updated: 2017-02-03Bibliographically approved

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Gabrielsson, Erik O.Hammarström, PerNilsson, K. Peter N.Berggren, Magnus

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